MacroGenics Announces Presentation of MGD019 Phase 1 Data at the ESMO Virtual Congress 2020

  • MGD019 well-tolerated with early signals of activity in advanced solid tumors not typically responsive to checkpoint inhibition
  • Recommended Phase 2 dose established for MSS CRC, NSCLC expansion cohorts
  • Presentation is available on-demand as part of the ESMO Virtual Congress 2020 

ROCKVILLE, MD, Sept. 20, 2020 (GLOBE NEWSWIRE) —

MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced clinical data from the dose escalation portion of a Phase 1 clinical trial of MGD019. The proffered paper session titled, “A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD019, an Investigational Bispecific PD-1 × CTLA-4 DART® Molecule in Patients with Advanced Solid Tumors,” was presented orally at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on September 20, 2020, by Dr. Manish R. Sharma, Associate Director of Clinical Research at START Midwest in Grand Rapids, Michigan.

MGD019, a bispecific PD-1 × CTLA-4 DART molecule, was designed to enhance CTLA-4 blockade on dual-expressing, tumor-infiltrating lymphocytes compared to a PD-1/CTLA-4 monoclonal antibody (mAb) combination therapy, while maintaining maximal PD-1 blockade on all PD-1-expressing cells. 

Forty-three patients were enrolled in the Phase 1 dose escalation study of MGD019 within a dose range of 0.03 – 10.0 mg/kg, administered every three weeks initially, in a population of heavily pre-treated patients representing a broad range of different types (23) of solid tumors. There were no dose-limiting toxicities (DLTs). A total of 28 patients were treated at doses ≥ 3.0 mg/kg administered every three weeks initially. MGD019 was well-tolerated in patients who received less than 10 mg/kg; the most common treatment-related adverse events over this dosing range were pruritus (23.3%), arthralgia (18.6%), fatigue (18.6%), rash (18.6%), nausea (16.3%) and infusion-related reaction (16.3%). Several Grade 3 adverse events were observed at the 10.0 mg/kg level; however, none were considered dose limiting.

In this study, sustained peripheral PD-1 blockade was evident at doses ≥ 1.0 mg/kg.  In addition, dose-dependent upregulation of the inducible costimulator (ICOS) molecule was evident in treated patients, including those who responded to MGD019 therapy.  This is consistent with the previously reported observation that anti-CTLA-4 therapy increases the frequency of CD4 T cells expressing the ICOS molecule.1

Of the 18 evaluable patients who received doses ≥ 3.0 mg/kg as of the July 21, 2020 cut-off date, four objective responses have been reported in this trial, including a confirmed complete response in metastatic castration-resistant prostate cancer (mCRPC), confirmed partial responses in microsatellite stable colorectal cancer (MSS CRC) and metastatic type AB thymoma, and an unconfirmed partial response in serous fallopian tube carcinoma.

“We are especially encouraged by the evidence of anti-tumor activity in patients treated with MGD019 who have cancers typically unresponsive to checkpoint inhibition. In addition, we are very pleased that MGD019 was well tolerated,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. “Based on the results presented today, we plan to expand the study initially in patients with MSS CRC and checkpoint-naïve non-small cell lung cancer at the recommended Phase 2 dose of 6.0 mg/kg.”

These results are available on-demand as part of the ESMO Virtual Congress 2020 Proffered Paper – Investigational Immunotherapy session on September 20, 2020 (Presentation # 1020O). In addition, Dr. Sharma’s slides can be accessed under “Events & Presentations” in the Investor Relations section of MacroGenics’ website at http://ir.macrogenics.com/events.cfm.

About MGD019

MGD019 is an investigational bispecific DART molecule that was designed to enable co-blockade of two immune checkpoint molecules co-expressed on T cells, PD-1 and CTLA-4.

About MacroGenics, Inc.

MacroGenics is a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. For more information, please see the Company’s website at www.macrogenics.com. MacroGenics and the MacroGenics logo are trademarks or registered trademarks of MacroGenics, Inc.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company’s strategy, future operations, clinical development of the Company’s therapeutic candidates, milestone or opt-in payments from the Company’s collaborators, the Company’s anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words “subject to”, “believe”, “anticipate”, “plan”, “expect”, “intend”, “estimate”, “project”, “may”, “will”, “should”, “would”, “could”, “can”, the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners and other matters that could affect the availability or commercial potential of the Company’s product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the novel coronavirus (referred to as COVID-19), and other risks described in the Company’s filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof.

1Cancer Immunol Res. 2013 Oct; 1(4): 229–234.

CONTACT: CONTACT:

Jim Karrels, Senior Vice President, CFO
MacroGenics, Inc.
1-301-251-5172, info@macrogenics.com

Chi-Med Highlights Surufatinib Phase III Results in Neuroendocrine Tumors at ESMO 2020 and Publications in The Lancet Oncology

― Phase III SANET-p demonstrated surufatinib reduces the risk of disease progression or death by 51% in patients with pancreatic neuroendocrine tumors (“NET”) ―

― SANET-p results complement previously presented positive Phase III SANET-ep results in patients with non-pancreatic NET, including across multiple subgroups ―

― Results of both SANET-p and SANET-ep studies published in The Lancet Oncology –

HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., Sept. 20, 2020 (GLOBE NEWSWIRE) — Hutchison China MediTech Limited (“Chi-Med”) (Nasdaq/AIM: HCM) today announces that positive results of the Phase III study of surufatinib in advanced neuroendocrine tumors – pancreatic (“SANET-p”) were presented as a proffered paper session at the European Society for Medical Oncology (“ESMO”) Virtual Congress 2020 (Abstract Number 1156O). Results from SANET-p, in addition to previously presented results from Phase III study of surufatinib in advanced neuroendocrine tumors – extra-pancreatic (“SANET-ep”), are published today in The Lancet Oncology.

“Surufatinib demonstrated statistically significant and clinically meaningful benefits in patients with advanced pancreatic NET. These results, combined with positive results from the parallel study of surufatinib in patients with non-pancreatic NET, support surufatinib as a promising treatment option for well-differentiated NET patients regardless of tumor origin,” commented Dr. Jianming Xu, lead investigator for the SANET-p study, Head of the Department of Gastrointestinal Oncology, The Fifth Medical Center, General Hospital of the PLA in Beijing.

As announced in January 2020, the Independent Data Monitoring Committee (“IDMC”) for the SANET-p trial recommended that the study stop early because it had met the pre-defined primary endpoint of progression free survival (“PFS”) during a planned interim analysis. At data cut-off as of November 11, 2019, 172 patients were randomized 2:1 to treatment with either 300 mg of surufatinib orally daily (N=113) or placebo control (N=59), on a 28-day cycle. Median PFS was 10.9 months for patients treated with surufatinib, as compared to 3.7 months for patients in the placebo group (hazard ratio [“HR”] 0.491; 95% confidence interval [“CI”] 0.391-0.755; p=0.0011). Benefit was observed across most major subgroups of pNET patients. Objective response rates (ORR) were 19.2%1 for the 104 efficacy evaluable patients in the surufatinib group versus 1.9%2 for the 53 efficacy evaluable patients in the placebo group, with a disease control rate (DCR) of 80.8% versus 66.0%, respectively. Most patients in the trial had Grade 2 disease with heavy tumor burden, including liver metastasis and multiple organ involvement. Efficacy was also supported by Blinded Independent Image Review Committee (BIIRC) assessment, with a median PFS of 13.9 months for surufatinib as compared to 4.6 months for placebo (HR 0.339; 95% CI 0.209-0.549; p<0.0001).

The safety profile of surufatinib was manageable and consistent with observations in prior studies. Treatment was well tolerated for most patients, with discontinuation rates as a result of treatment emergent adverse events of 10.6% in the surufatinib group as compared to 6.8% in the placebo group.

In the U.S., the Food and Drug Administration (“FDA”) granted surufatinib two Fast Track Designations, for both the non-pancreatic NET and pancreatic NET development programs, and Orphan Drug Designation for pancreatic NET development. A rolling new drug application (“NDA”) submission is being prepared, to be followed by a marketing authorization application (“MAA”) submission to the European Medicines Agency (“EMA”) in Europe, based on the robust data from the two studies and the ongoing multi-cohort Phase Ib study in the U.S. In December 2019, an NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was granted Priority Review status by the China National Medical Products Administration (“NMPA”). A second NDA for surufatinib for the treatment of patients with advanced pancreatic NET has also been accepted by the NMPA.

About NET

NET form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. NET are typically classified as pancreatic NET or non-pancreatic NET. Approved targeted therapies include Sutent® and Afinitor® for pancreatic NET, or well-differentiated, non-functional gastrointestinal or lung NET.

According to Frost and Sullivan, there were 19,000 newly diagnosed cases of NET in the U.S. in 2018. Importantly, NET are associated with a relatively long duration of survival compared to other tumors. As a result, there were approximately 141,000 estimated patients living with NET in the U.S. in 2018.

In China, there were approximately 67,600 newly diagnosed NET patients in 2018 and, considering the current incidence to prevalence ratio in China, potentially as many as 300,000 patients living with the disease in the country.3  

About Surufatinib

Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Chi-Med currently retains all rights to surufatinib worldwide.

About Surufatinib Development

NET in the U.S. and Europe: In the U.S., surufatinib was granted Fast Track Designations for development in pancreatic and non-pancreatic (extra-pancreatic) NET in April 2020, and Orphan Drug Designation for pancreatic NET in November 2019. A U.S. FDA NDA submission is being prepared, to be followed by a MAA submission to the EMA in Europe. The basis to support these filings includes the completed SANET-ep and SANET-p studies, along with existing data from surufatinib in U.S. non-pancreatic and pancreatic NET patients (clinicaltrials.gov identifier: NCT02549937).

Non-pancreatic NET in China: In November 2019, a NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was accepted for review by the NMPA and granted Priority Review status in December 2019. The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in patients with advanced non-pancreatic NET in China for whom there is no effective therapy. A 198-patient interim analysis was conducted in June 2019, leading the IDMC to determine that the study met the pre-defined primary endpoint of PFS and should be stopped early. The positive results of this trial were highlighted in an oral presentation at the 2019 ESMO Congress (clinicaltrials.gov identifier: NCT02588170) and published in The Lancet Oncology in September 2020. 4 Median PFS was 9.2 months for patients treated with surufatinib, as compared to 3.8 months for patients in the placebo group (HR 0.334; 95% CI: 0.223-0.499; p<0.0001).

Pancreatic NET in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic NET in China. Following an interim analysis review conducted in January 2020 by the IDMC that recommended the registrational study be terminated early as the pre-defined primary endpoint of PFS had already been met (clinicaltrials.gov identifier: NCT02589821), leading to a second NDA accepted by the China NMPA. The results of this study were presented at the ESMO Virtual Congress 2020 and published simultaneously in The Lancet Oncology. 5

Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is overall survival (OS) (clinicaltrials.gov identifier NCT03873532).

Immunotherapy combinations: We have entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd.), Tuoyi® (toripalimab, developed by Shanghai Junshi Biosciences Co. Ltd.) and Tyvyt® (sintilimab, developed by Innovent Biologics, Inc.), which are approved in China.

About Chi-Med

Chi-Med (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit: www.chi-med.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations regarding the submission of an NDA for surufatinib for the treatment of NET in the U.S., China and other jurisdictions, the therapeutic potential of surufatinib for the treatment of patients with NET, the further clinical development for surufatinib in this and other indications, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of the clinical data to support NDA approval of surufatinib for the treatment of patients with NET in the U.S. and China or other jurisdictions, its potential to gain expeditious approvals from regulatory authorities, the safety profile of surufatinib, enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of surufatinib, including as a combination therapy, to meet the primary or secondary endpoint of a study, its ability to fund, implement and complete its further clinical development and commercialization plans for surufatinib, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of capecitabine, tislelizumab, Tuoyi®, and Tyvyt® as combination therapeutics with surufatinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

CONTACTS

Investor Enquiries  
Mark Lee, Senior Vice President +852 2121 8200
Annie Cheng, Vice President +1 (973) 567 3786
   
Media Enquiries  
Americas – Brad Miles, Solebury Trout +1 (917) 570 7340 (Mobile)
bmiles@troutgroup.com
Europe – Ben Atwell / Alex Shaw, FTI Consulting +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)
Chi-Med@fticonsulting.com
Asia – Joseph Chi Lo / Zhou Yi, Brunswick +852 9850 5033 (Mobile), jlo@brunswickgroup.com / +852 9783 6894 (Mobile), yzhou@brunswickgroup.com
   
Nominated Advisor  
Freddy Crossley / Atholl Tweedie, Panmure Gordon (UK) Limited +44 (20) 7886 2500

___________________________________________

1 Responses in the surufatinib group included 13 confirmed partial responses and 7 unconfirmed partial responses.
2 There was 1 confirmed partial response in the placebo group.
3 According to Frost & Sullivan, in 2018, there were 19,000 newly diagnosed cases of NETs in the U.S and an estimated 141,000 patients living with NETs. The current incidence to prevalence ratio in China is estimated at 4.4, lower than the 7.4 ratio in the U.S. due to lower access to treatment options.
4 Xu J, Shen L, Zhou Z, et al. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study [published online ahead of print, 2020 Sep 20]. Lancet Oncol. 2020;S1470-2045(20)30496-4. DOI: 10.1016/S1470-2045(20)30496-4.
5 Xu J, Shen L, Bai C, et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study [published online ahead of print, 2020 Sep 20]. Lancet Oncol. 2020; S1470-2045(20)30493-9. DOI: 10.1016/S1470-2045(20)30493-9.

Sotorasib (AMG 510) Shows Promising Results in Some Patients With Solid Tumors, Suggests a Study With City of Hope as a Co-Lead Author

Participants with advance non-small cell lung cancer and colorectal cancer experienced the greatest benefits in this first-in-human phase 1 clinical trial.


DUARTE, Calif.–(BUSINESS WIRE)–#CityofHope–A phase 1 clinical trial of sotorasib (AMG 510) in patients with heavily pretreated advanced solid tumors shows encouraging anti-cancer activity, especially in lung and colorectal cancers, reports a new study led by City of Hope and other renowned comprehensive cancer centers.

The multisite clinical trial included 129 metastatic cancer patients who had received an average of three prior therapies. These patients all had the mutated KRAS G12C gene, which increases the chances that an individual will be diagnosed with an aggressive cancer resistant to treatment.

“We have finally shown that RAS targeting and inhibition is feasible. We hope that this will be the first step amongst many to effectively treat RASmutant cancers, one of the most common drivers of cancer,” said Marwan Fakih, M.D., medical oncologist at City of Hope and co-lead author of the New England Journal of Medicine study that published today.

The KRAS gene, discovered nearly 40 years ago, is known as an oncogene. When mutated, KRAS could activate a pathway that turns normal cells cancerous. This gene belongs to the RAS gene family, which is responsible for more than 30% of all human cancers, according to the National Cancer Institute.

“KRAS mutations have been linked with worse treatment outcomes in a variety of cancers, including lung and colorectal cancers,” Fakih added. “This proof-of-concept study has, in some cases, demonstrated a median progression-free survival that is two times longer than what we encounter in patients today.”

The purpose of the clinical trial was to test the safety of various doses of sotorasib (180mg, 360mg, 720mg and 960mg), which were taken orally once a day. Patients had refractory metastatic non-small cell lung cancer (59 participants), colorectal cancer (42 participants) or other tumor types (28 participants). Their average age was 62, and the median follow-up was 12 months.

Sotorasib is a small molecule that inhibits KRAS G12C by plugging up a specific pocket (P2), inhibiting the ability of this mutated KRAS protein from driving tumor growth and spread. Current studies show that the drug, while able to target many cancers, appears to be most potent in non-small cell lung cancer, where KRAS G12C mutations exist in about 13% of patients.

The KRAS G12C inhibitor sotorasib produced lasting clinical benefits with mostly minor side effects that affected the gastrointestinal tract and included diarrhea (30%), fatigue (23%) and nausea (21%). Although trial patients had stubborn cancers resistant to standard-of-care treatments, those with non-small cell lung cancer had a 32% response rate with the majority (88%) achieving disease control for at least a few months. Their median progression-free survival was 6.3 months. This is a great improvement considering that later lines of treatment in non-small cell lung cancer are typically associated with response rates of only 9-18% and a median progression-free survival of approximately three months.

The other group that saw notable benefit were patients with refractory metastatic colorectal cancer — a response rate of about 7%, disease control rate of 74% and major tumor shrinkage in 7% of the group, Fakih said. The median progression-free survival was four months. In comparable lines of treatment, response rates are rarely experienced, and the median progression-free survival is approximately two months.

“The benefits of sotorasib appear to be quite durable with at least half of metastatic colorectal cancer patients still experiencing disease control four months after the start of treatment,” Fakih said. “When you consider the poor prognosis for the metastatic setting and the lack of effective treatments for this population, controlling tumor progression for a few additional months with an oral therapy is a significant and meaningful outcome.”

Treatment was discontinued in 107 patients (83%), mostly because of disease progression. Fifty-four patients had died, a reasonable outcome given the prognosis and late stage of the disease.

Fakih, director of the Gastrointestinal Cancer Program at City of Hope, is involved in two sotorasib (AMG 510) clinical trials with a total of six treatment arms to evaluate use of sotorasib as a monotherapy or combination treatment in patients with non-small cell lung cancer, colorectal cancer and other solid tumors.

The inconsistency in tumor response between non-small cell lung cancer and colorectal cancer suggests that KRAS G12C inhibition is not sufficient for colorectal cancer and that additional cancer-causing pathways must be switched off, Fakih said. Combining sotorasib with other therapies that block the epidermal growth factor receptor (EGFR), a protein whose overexpression has been linked to many cancers, is a promising path forward that is under investigation, he added.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nation’s “Best Hospitals” in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

The study was supported by Amgen Inc., Cancer Prevention & Research Institute of Texas (RP150535, P30 CA016672), Fox Chase Cancer Center’s National Institutes of Health grant (P30 CA006927), Memorial Sloan Kettering Cancer Center’s NIH grant (P30 CA008748), NIH/NCI (1R01CA23074501, 1R01CA23026701A1), The Pew Charitable Trusts and the Damon Runyon Cancer Research Foundation.

Contacts

Zen Vuong

626-409-9367

zvuong@coh.org

Merck and Eisai Present First-Time Data From Two Studies Evaluating KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) in Seven Different Tumor Types at ESMO Virtual Congress 2020

New Results Include Findings From the Phase 2 LEAP-004 Trial Showing an ORR of 21.4% in Patients With Unresectable or Advanced Melanoma Who Had Previously Progressed on an Anti-PD-1/PD-L1 Therapy

KENILWORTH, N.J., & WOODCLIFF LAKE, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced new investigational data from two trials under the LEAP (LEnvatinib And Pembrolizumab) clinical program evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai. In the Phase 2 LEAP-004 trial, KEYTRUDA plus LENVIMA showed an objective response rate (ORR) of 21.4% (95% CI: 13.9-30.5) in patients with unresectable or advanced melanoma who had previously progressed on an anti-PD-1/PD-L1 therapy. In the Phase 2 LEAP-005 trial, KEYTRUDA plus LENVIMA demonstrated an ORR that ranged from 9.7-32.3% (95% CI: 2.0-51.4) in previously treated patients with triple-negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (non-microsatellite instability-high [non-MSI-H]/mismatch repair proficient [pMMR]), glioblastoma multiforme (GBM) and biliary tract cancer (BTC). Results from LEAP-004 (Abstract #LBA44) and LEAP-005 (Abstract #LBA41) were accepted as late-breaking abstracts and are being presented in proffered paper presentations at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“These new data from our LEAP clinical program show encouraging activity across several aggressive cancer types and expand our knowledge about the potential of KEYTRUDA plus LENVIMA to help a range of patients with these cancers,” said Dr. Scot Ebbinghaus, Vice President, Clinical Research, Merck Research Laboratories. “This is the first time that clinical data from two LEAP trials are being presented, reflecting important progress we are making to explore the potential of this combination for patients in need of new options, particularly those with advanced melanoma who have progressed on an anti-PD-1 or PD-L1 therapy.”

“We are encouraged by the growing body of research that we have seen to date, now in 13 different cancers, supporting the potential of the KEYTRUDA plus LENVIMA combination, which we’re currently evaluating in 19 clinical trials,” said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. “These data not only help advance our understanding of the regimen but also fuel our deep-seated determination to work to address the unmet needs of these patients.”

LEAP-004 Trial Design and Data (Abstract #LBA44)

LEAP-004 (ClinicalTrials.gov, NCT03776136) is a Phase 2, single-arm, open-label trial evaluating KEYTRUDA in combination with LENVIMA in patients with unresectable or advanced melanoma who had progressed on an anti-PD-1/PD-L1 therapy within 12 weeks. Patients were treated with LENVIMA 20 mg orally once daily until unacceptable toxicity or disease progression in combination with KEYTRUDA 200 mg intravenously every three weeks until unacceptable toxicity or disease progression for up to 35 cycles (approximately two years). The primary endpoint is ORR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by blinded independent central review (BICR). Secondary endpoints include progression-free survival (PFS) and duration of response (DOR) per RECIST v1.1 by BICR, overall survival (OS) and safety.

At data cutoff (June 10, 2020), a total of 103 patients were enrolled and treated. With a median duration of follow-up of 12 months (range: 8.7-15.6), KEYTRUDA plus LENVIMA demonstrated an overall ORR by BICR of 21.4% (n=22) (95% CI: 13.9-30.5), with a complete response rate of 1.9% (n=2) and a partial response rate of 19.4% (n=20). In the total study population, the median DOR was 6.3 months (range: 2.1+ to 11.1+), with 72.6% (95% CI: 46.2-87.6) of responses lasting for at least six months. Median PFS was 4.2 months (range: 3.5 to 6.3), with 73.8% of patients experiencing disease progression or death, and the nine-month PFS rate was 26.2% (95% CI: 17.4-35.9). Median OS was 13.9 months (range: 10.8-not reached [NR]), with death occurring in 44.7% of patients, and the nine-month OS rate was 65.4% (95% CI: 55.2-73.8).

The exploratory analysis showed that specifically in the 29 patients whose disease progressed after an anti-PD-1/L1 therapy plus an anti-CTLA-4 therapy, the ORR by BICR was 31.0% (95% CI: 15.3-50.8), with a complete response rate of 3.4% (n=1) and a partial response rate of 27.6% (n=8), and the disease control rate (DCR) by BICR was 62.1% (95% CI: 42.3-79.3). In the total study population, the DCR by BICR was 65.0% (95% CI: 55.0-74.2).

Treatment-related adverse events (TRAEs) led to discontinuation of KEYTRUDA and/or LENVIMA in 7.8% of patients. Grade 3-5 TRAEs occurred in 44.7% of patients (Grade 3: 39.8%; Grade 4: 3.9%; Grade 5: 1.0%), and serious TRAEs occurred in 18.4% of patients. The most common TRAEs of any grade occurring in at least 30% of the overall study population were hypertension (56.3%), diarrhea (35.9%), nausea (34.0%), hypothyroidism (33.0%) and decreased appetite (31.1%).

LEAP-005 Trial Design and Data (Abstract #LBA41)

LEAP-005 (ClinicalTrials.gov, NCT03797326) is a Phase 2, single-arm, open-label trial evaluating KEYTRUDA in combination with LENVIMA in patients with select previously treated advanced solid tumors. The study cohorts are TNBC, ovarian cancer, gastric cancer, colorectal cancer (non-MSI-H/pMMR), GBM and BTC. Patients were treated with LENVIMA 20 mg orally once daily until unacceptable toxicity or disease progression in combination with KEYTRUDA 200 mg intravenously every three weeks until unacceptable toxicity or disease progression for up to 35 cycles (approximately two years). The primary endpoints are ORR per RECIST v1.1 as assessed by BICR or Response Assessment in Neuro-Oncology (RANO) criteria (for GBM only) as assessed by BICR, and safety. Secondary endpoints include DCR per RECIST v1.1 by BICR or RANO (for GBM only) by BICR, DOR per RECIST v1.1 by BICR or RANO (for GBM only) by BICR, PFS per RECIST v1.1 by BICR or RANO (for GBM only) by BICR, and OS.

At data cutoff (April 10, 2020), a total of 187 patients were enrolled and treated. The confirmed ORR after a median duration of follow-up of 8.6 months (range: 1.9-13.1) for the six different tumor types, as well as additional efficacy and safety results, showed:

 

2L/3L TNBC

(n=31)

4L

Ovarian

(n=31)

3L Gastric

(n=31)

3L Colorectal

(n=32)

2L

BTC

(n=31)

2L

GBM

(n=31)

ORR, %

(95% CI)

29.0 (14.2-48.0)

32.3 (16.7-51.4)

9.7 (2.0-25.8)

21.9 (9.3-40.0)

9.7 (2.0-25.8)

16.1 (5.5-33.7)

DCR, %

(95% CI)

58.1 (39.1-75.5)

74.2 (55.4-88.1)

48.4 (30.2-66.9)

46.9 (29.1-65.3)

67.7 (48.6-83.3)

58.1 (39.1-75.5)

DOR, median (range), months

NR (0.0+ to 8.4+)

NR (1.5+ to 7.9+)

NR (2.1+ to 2.3+)

NR (2.1+ to 10.4+)

5.3 (2.1+ to 6.2)

3.2 (2.5 to 4.9+)

Grade ≥3 TRAEs, % (n)

55 (17)

68 (21)

42 (13)

50 (16)

48 (15)

35 (11)

Death due to a TRAE, % (n)

3 (1)

3 (1)

3 (1)

3 (1)

0 (0)

3 (1)

Discontinued due to a TRAE, % (n)

10 (3)

13 (4)

6 (2)

9 (3)

6 (2)

6 (2)

+, no progressive disease (PD) as of last disease assessment; DCR, disease control rate (best confirmed response: complete/partial response; stable disease); DOR, duration of response; NR, not reached

The most common TRAEs of any grade occurring in at least 20% of the overall study population were hypertension (39.0%), fatigue (29.4%), diarrhea (26.7%), decreased appetite (25.1%), hypothyroidism (27.8%) and nausea (21.9%). The study is ongoing and will be expanded to enroll approximately 100 patients in each cohort.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

  • solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
  • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Endometrial Carcinoma

KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA® (pembrolizumab)

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function.

Contacts

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Eisai Inc. Media Relations
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TAGRISSO Reduced the Risk of Disease Recurrence in the Brain by 82% in the Adjuvant Treatment of Early-Stage EGFR-Mutated Lung Cancer

ADAURA Phase III trial data at ESMO reinforce the proven clinical activity of TAGRISSO in treating central nervous system metastases

WILMINGTON, Del.–(BUSINESS WIRE)–Results from a prespecified exploratory analysis of the positive ADAURA Phase III trial showed AstraZeneca’s TAGRISSO® (osimertinib) demonstrated a clinically meaningful improvement in central nervous system (CNS) disease-free survival (DFS) in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC), after complete tumor resection.

While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease.1-3 CNS recurrence, when cancer spreads to the brain, is a frequent complication of EGFRm NSCLC and these patients have an especially poor prognosis.4,5

Results were presented on September 19, 2020 during the Presidential Symposium of the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (abstract #LBA1) and simultaneously published with the primary results in The New England Journal of Medicine.

This analysis showed that fewer patients treated with TAGRISSO in the adjuvant setting had recurrence events or deaths compared to placebo (11% versus 46%). Among patients whose cancer recurred, 38% of those treated with TAGRISSO had a metastatic recurrence compared to 61% of patients on placebo. TAGRISSO showed an 82% reduction in the risk of CNS recurrence or death (based on a hazard ratio [HR] of 0.18; 95% confidence interval [CI] 0.10-0.33; p<0.0001). Median CNS DFS was not yet reached in either arm.

In a post-hoc analysis, the estimated probability of observing disease recurrence in the brain at 18 months for patients treated with TAGRISSO was less than 1% versus 9% for placebo among patients who had not experienced another type of recurrence. On the primary endpoint of DFS in patients with Stage II and IIIA disease, TAGRISSO in the adjuvant setting reduced the risk of disease recurrence or death by 83% (HR 0.17; 95% CI 0.12-0.23; p<0.0001).

Masahiro Tsuboi, MD, PhD, director of the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East in Japan, and a principal investigator in the ADAURA Phase III trial, said: “It’s time to change the notion that treatment for early-stage EGFR-mutated lung cancer ends after surgery, since recurrence rates are still very high even after adjuvant chemotherapy. These new data showing low rates of recurrence, particularly in the brain, combined with the remarkable disease-free survival benefit, clearly demonstrate that TAGRISSO provides patients with more time living cancer-free.”

José Baselga, Executive Vice President, Oncology R&D, said: “Once lung cancer has spread to the brain, outcomes are typically devastating for patients. We are now seeing TAGRISSO expanding on its proven efficacy in treating progression in the brain in the metastatic setting as a result of its ability to cross the blood-brain barrier. The striking new data show that TAGRISSO prevents the development of brain metastases in patients with early disease and reinforce that this medicine is truly transformative for patients with EGFR-mutated lung cancer. TAGRISSO should become the standard of care in the adjuvant setting, just as it is for patients with metastatic disease around the world.”

Summary of exploratory results on CNS recurrence in the ADAURA Phase III trial

 

TAGRISSO

n=339

Placebo

n=343

CNS DFS

 

HR (95% CI)

0.18 (0.10-0.33);

p-value

p<0.0001

CNS DFS events, patients (%):

6 (2%)

39 (11%)

CNS recurrence

4 (1%)

33 (10%)

Deathi

2 (1%)

6 (2%)

DFS events, patients (%):

37 (11%)

159 (46%)

Type of disease

recurrence

n=37

n=157

Local/regional only

23 (62%)

61 (39%)

Distant

14 (38%)

96 (61%)

Deathii

0

2 (1%)

i. Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.

ii. Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.

The safety and tolerability of TAGRISSO in this trial was consistent with previous trials in the metastatic EGFRm NSCLC setting. Adverse events at Grade 3 or higher from all causes occurred in 10% of patients in the TAGRISSO arm versus 3% in the placebo arm as assessed by investigators.

TAGRISSO is not currently approved in the adjuvant setting in any country. TAGRISSO received Breakthrough Therapy Designation in July 2020 for the adjuvant treatment of patients with early-stage EGFRm NSCLC after complete tumor resection with curative intent. TAGRISSO is approved for the 1st-line treatment of patients with metastatic EGFRm NSCLC and for the treatment of metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

TAGRISSO IMPORTANT SAFETY INFORMATION

  • There are no contraindications for TAGRISSO
  • Interstitial lung disease (ILD)/pneumonitis occurred in 3.9% of the 1142 TAGRISSO-treated patients; 0.4% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
  • Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 1142 TAGRISSO-treated patients in clinical trials, 0.9% were found to have a QTc >500 msec, and 3.6% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
  • Cardiomyopathy occurred in 2.6% of the 1142 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.9% of 908 patients who had baseline and at least one follow-up LVEF assessment. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
  • Keratitis was reported in 0.7% of 1142 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
  • Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed
  • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
  • Most common adverse reactions (≥20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue and decreased appetite

INDICATIONS

  • TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

Please see complete Prescribing Information, including Patient Information.

About Lung cancer

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.6 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.7 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3

For those with resectable tumors, the majority of patients eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.8 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.9,10

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.11-13 These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signaling pathways that drive the growth of tumor cells.14

About ADAURA

ADAURA is a randomized, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with TAGRISSO 80 mg once-daily oral tablets or placebo for three years or until disease recurrence.

The trial enrolled in more than 200 centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint is DFS in Stage II and IIIA patients and a key secondary endpoint is DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess OS.

About TAGRISSO

TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. TAGRISSO 40 mg and 80 mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm advanced NSCLC and EGFR T790M mutation-positive advanced NSCLC.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

AstraZeneca aims to address the unmet needs of patients with EGFRm tumors as a genetic driver of disease with the approved medicines gefitinib and TAGRISSO and its ongoing Phase III trials LAURA, NeoADAURA and FLAURA2.

AstraZeneca is committed to addressing tumor mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD, which test TAGRISSO in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

References

1. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137:1191-1198.

2. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:196-198.

3. Datta D, et al. Preoperative Evaluation of Patients Undergoing Lung Resection Surgery. Chest. 2003;123:2096–2103.

4. Rangachari D, et al. Brain Metastases in Patients with EGFR-Mutated or ALK-Rearranged Non-Small-Cell Lung Cancers. Lung Cancer. 2015;88:108–111.

5. Ali A, et al. Survival of Patients with Non-small-cell Lung Cancer After a Diagnosis of Brain Metastases. Curr Oncol. 2013;20(4):e300-e306.

6. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed September 2020.

7. LUNGevity Foundation. Types of Lung Cancer. Available at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer. Accessed September 2020.

8. Pignon JP et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552-3559.

9. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis. 2016;8:S494-S497.

10. LUNGevity Foundation. Screening and Early Detection. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection#1. Accessed September 2020.

11. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013;6:2800-2812.

12. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011;29:2121-2127.

13. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66:79-89.

14. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

Contacts

Media Inquiries
Michele Meixell +1 302 885 2677

Brendan McEvoy +1 302 885 2677

Immunomedics Announces Positive Results from Pivotal Phase 2 TROPHY U-01 Study of Trodelvy™ in Metastatic Urothelial Cancer

Trodelvy achieves a 27 percent overall response rate and a 5.9-month median duration of response in heavily-pretreated patients with metastatic urothelial cancer (mUC)

sBLA submission for accelerated approval expected in fourth quarter 2020, pending FDA final guidance

Phase 3 TROPiCS-04 study in third-line mUC underway

Company to host conference call and webcast today at 2:00 p.m. Eastern Time

MORRIS PLAINS, N.J., Sept. 19, 2020 (GLOBE NEWSWIRE) — Immunomedics, Inc. (NASDAQ: IMMU) (“Immunomedics” or the “Company”), a leading biopharmaceutical company in the area of antibody-drug conjugates, today announced positive results from cohort 1 of cisplatin-eligible patients in the pivotal Phase 2 TROPHY U-01 study of Trodelvy (sacituzumab govitecan-hziy) in metastatic urothelial cancer (mUC). Results confirm the interim findings and prior Phase 1/2 study results showing Trodelvy has significant activity and is safe in patients with heavily-pretreated mUC who progressed on both platinum-based chemotherapy and checkpoint inhibitors (CPI).

“Given that only about 10 percent of patients with mUC who have cancer progression after platinum-based and CPI therapy are expected to respond to single-agent chemotherapy with approximately two to three months of median progression-free survival, today’s compelling results with sacituzumab govitecan offer patients and families new hope,” commented Yohann Loriot, MD, PhD, Institut de Cancérologie Gustave Roussy, Villejuif, France, who gave the late-breaking oral presentation of the pivotal study at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

Results for cohort 1 of TROPHY U-01 are summarized in the table below. As of data cutoff on May 18, 2020, eight of the 31 responders have an ongoing response and remain on treatment. Trodelvy has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) in this indication.

Parameter Cohort 1 (N=113)
Median prior anticancer regimens, n (range) 3.0 (1–8)
Overall response rate*, n (%) [95% CI] 31 (27) [19, 37]
Complete response, n (%) 6 (5)
Partial response, n (%) 25 (22)
Median duration of response*, months [95% CI] (Range) 5.9 [4.70, 8.60] (1.4–11.7)
Median time to onset of response*, months (Range) 1.6 (1.2–5.5)
Median progression-free survival, months (95% CI) 5.4 (3.5, 6.9)
Median overall survival, months (95% CI) 10.5 (8.2, 12.3)

* Based on blinded independent central assessment per RECIST v1.1

“We believe that Trodelvy may offer a new treatment option for patients with mUC based on the successful data readout today,” remarked Dr. Loretta M. Itri, Chief Medical Officer of Immunomedics. “While we are seeking guidance from the FDA on the registrational pathway, the new Phase 3 TROPiCS-04 study in third-line mUC has been reviewed by FDA, is under review by the European Medicines Agency, and is currently in initiation phase.”

Trodelvy continued to demonstrate a tolerable and predictable safety profile consistent with previous observations in mUC and other tumor types. Treatment-related Grade 3 and 4 adverse events were mostly hematologic and gastrointestinal related, including neutropenia (34%) and diarrhea (10%). Seven patients (6%) discontinued treatment due to adverse events, three of whom due to neutropenia or its complications. There was one treatment-related death from sepsis due to febrile neutropenia. There were no grade 2 or above events of neuropathy or rash, and no cases of interstitial lung disease reported.

Conference Call

The Company will host a conference call and live audio webcast with key opinion leaders today at 2:00 p.m. Eastern Time to discuss the TROPHY U-01 results and provide a corporate update. To access the conference call supported with slides, please dial (877) 303-2523 or (253) 237-1755 using the Conference ID 1871157. The conference call with supporting slides will be webcast via the Investors page on the Company’s website at https://immunomedics.com/investors/. Approximately two hours following the live event, a webcast replay of the conference call will be available on the Company’s website for approximately 30 days.

About Immunomedics

Immunomedics is a leader in next-generation antibody-drug conjugate (ADC) technology, committed to help transform the lives of people with hard-to-treat cancers. Our proprietary ADC platform centers on using a novel linker that does not require an enzyme to release the payload to deliver an active drug inside the tumor cell and the tumor microenvironment, thereby producing a bystander effect. Trodelvy, our lead ADC, is the first ADC the FDA has approved for the treatment of people with metastatic triple-negative breast cancer and is also the first FDA-approved anti-Trop-2 ADC. For additional information on the Company, please visit its website at https://immunomedics.com/. The information on its website does not, however, form a part of this press release.

Cautionary note regarding forward-looking statements

This release, in addition to historical information, may contain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding expectations for achieving full FDA approval based on our confirmatory data for TRODELVY and the Company’s development of TRODELVY for additional indications, clinical trials (including the funding therefor, anticipated patient enrollment, trial outcomes, timing or associated costs), regulatory applications and related timelines, including the filing and approval timelines for BLAs and BLA supplements, out-licensing arrangements, forecasts of future operating results, potential collaborations, capital raising activities, and the timing for bringing any product candidate to market, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, the Company’s reliance on third-party relationships and outsourcing arrangements (for example in connection with manufacturing, logistics and distribution, and sales and marketing) over which it may not always have full control, including the failure of third parties on which the Company is dependent to meet the Company’s business and operational needs for investigational or commercial products and, or to comply with the Company’s agreements or laws and regulations that impact the Company’s business; the Company’s ability to meet post-approval compliance obligations (on topics including but not limited to product quality, product distribution and supply chain requirements, and promotional and marketing compliance); imposition of significant post-approval regulatory requirements on our products, including a requirement for a post-approval confirmatory clinical study, or failure to maintain or obtain full regulatory approval for the Company’s products, if received, due to a failure to satisfy post-approval regulatory requirements, such as the submission of sufficient data from a confirmatory clinical study; the uncertainties inherent in research and development; safety and efficacy concerns related to the Company’s products and product candidates; uncertainties in the rate and degree of market acceptance of products and product candidates, if approved; inability to create an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure for distribution of the Company’s products and product candidates, if approved; inaccuracies in the Company’s estimates of the size of the potential markets for the Company’s products and product candidates or limitations by regulators on the proposed treatment population for the Company’s products and product candidates; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of the Company’s products and product candidates; the Company’s dependence on business collaborations or availability of required financing from capital markets, or other sources on acceptable terms, if at all, in order to further develop our products and finance our operations; new product development (including clinical trials outcome and regulatory requirements/actions); the risk that we or any of our collaborators may be unable to secure regulatory approval of and market our drug candidates; risks relating to the COVID-19 pandemic in the U.S. and around the world; risks associated with litigation to which the Company is or may become a party, including the cost and potential reputational damage resulting from such litigation; loss of key personnel; competitive risks to marketed products; and the Company’s ability to repay its outstanding indebtedness, if and when required, as well as the risks discussed in the Company’s filings with the Securities and Exchange Commission. The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.

For More Information:

Dr. Chau Cheng
(862) 260-3727
ccheng@immunomedics.com

For Media Inquiries:

Darren Opland, Ph.D.
(646) 627-8387
Darren@lifescipublicrelations.com

Trodelvy™ Significantly Extends Survival in Phase 3 ASCENT Study of Metastatic Triple-Negative Breast Cancer

Trodelvy significantly reduced the risk of death by 52 percent, with a median overall survival (OS) of 12.1 months compared to 6.7 months for standard single-agent chemotherapy

Trodelvy is the first ADC to significantly improve OS in metastatic triple-negative breast cancer (mTNBC)

sBLA for full approval to be submitted in fourth quarter 2020 under RTOR process

Company to host conference call and webcast today at 2:00 p.m. Eastern Time

MORRIS PLAINS, N.J., Sept. 19, 2020 (GLOBE NEWSWIRE) — Immunomedics, Inc. (NASDAQ: IMMU) (“Immunomedics” or the “Company”), a leading biopharmaceutical company in the area of antibody-drug conjugates, today announced that results from the confirmatory Phase 3 ASCENT study showed that Trodelvy (sacituzumab govitecan-hziy) significantly extended overall survival (OS) and improved overall response rate (ORR) and clinical benefit rate (CBR), compared to treatment of choice (TPC) standard single-agent chemotherapy in brain metastases-negative patients with mTNBC who had previously received at least two prior therapies for metastatic disease. These results will be presented today as a late-breaking abstract (Abstract# LBA17) at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“The randomized Phase 3 study results confirm that sacituzumab govitecan should be considered as a new standard of care in patients with third-line mTNBC,” stated Aditya Bardia, MD, MPH, Director of Precision Medicine at the Center for Breast Cancer, Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School, who will give an oral presentation of the study at the ESMO Congress. “We wish to express our gratitude to the patients and their caregivers for their valuable contribution, as well as the dedicated clinical trial investigators and their devoted team members for making the ASCENT trial possible. Ongoing studies are evaluating sacituzumab govitecan in earlier lines of therapy, including the neoadjuvant and adjuvant settings, in combination with other targeted agents, and in patients with hormone receptor-positive, human epidermal growth factor 2-negative metastatic breast cancer, which will help accelerate our efforts to further improve outcomes for patients with breast cancer.”

Despite having received a median of four prior anticancer regimens, patients treated with Trodelvy in the ASCENT study showed a statistically significant and clinically meaningful improvement in OS with a median of 12.1 months (95% confidence interval (CI), 10.7-14.0) versus 6.7 months (95% CI, 5.8-7.7) for chemotherapy, with a hazard ratio of 0.48 (95% CI, 0.38-0.59; p<0.0001). Trodelvy also demonstrated a statistically significant improvement in ORR (35%) and CBR (45%) compared to chemotherapy (5% and 9%, respectively). Ten complete responses were observed (4%) in the Trodelvy arm compared with two (1%) in the control group. As of data cutoff on March 11, 2020, 15 patients continued to receive Trodelvy treatment while no patient remained on study in the TPC control arm.

“We believe these remarkable results should facilitate the establishment of Trodelvy as a new standard of care in patients with third-line mTNBC,” said Dr. Loretta M. Itri, Chief Medical Officer of Immunomedics. “We are working very collaboratively with FDA under the RTOR program to submit a supplemental Biologics License Application to have Trodelvy’s label expanded to include these confirmatory new data. Additionally, we plan to submit a Marketing Authorization Application to the European Medicines Agency in the first half of 2021 in order to make this important new treatment available to mTNBC patients in Europe.”

Trodelvy was well tolerated by patients in the ASCENT study, with a manageable safety profile consistent with the U.S. Food and Drug Administration (FDA)-approved label; no new safety signals were observed in the ASCENT study. Adverse events leading to treatment discontinuation were low and similar (Trodelvy 4.7% vs TPC 5.4%) in both arms of the study.

“We are delighted to witness the clinically meaningful survival benefit Trodelvy is bringing to mTNBC patients. These outstanding results have inspired us to fully demonstrate the potential of this valuable new treatment to improve the outlook of cancer patients worldwide,” commented Dr. Behzad Aghazadeh, Executive Chairman of Immunomedics.

Trodelvy was approved as a third-line treatment for adult patients with mTNBC under the FDA’s Accelerated Approval Program and carries a black box warning for severe neutropenia and severe diarrhea. The most common adverse reactions occurring in 25 or more percent of patients included nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash and abdominal pain. The most common Grade 3 or 4 adverse events occurring in more than 5 percent of patients were neutropenia, white blood cell count decreased, anemia, hypophosphatemia, diarrhea, fatigue, nausea and vomiting. Two percent of patients discontinued treatment due to adverse events. There were no deaths related to treatment and no severe cases of neuropathy or interstitial lung disease.1

Conference Call

The Company will host a conference call and live audio webcast with key opinion leaders today at 2:00 p.m. Eastern Time to discuss the ASCENT results and provide a corporate update. To access the conference call supported with slides, please dial (877) 303-2523 or (253) 237-1755 using the Conference ID 1871157. The conference call with supporting slides will be webcast via the Investors page on the Company’s website at https://immunomedics.com/investors/. Approximately two hours following the live event, a webcast replay of the conference call will be available on the Company’s website for approximately 30 days.

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer, accounting for up to 20 percent of all breast cancers. The disease is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American and Hispanic women. TNBC cells do not have estrogen or progesterone hormone receptors, or very much of the human epidermal growth factor receptor 2 – hence the term triple negative. This means that medicines that target these receptors are not typically effective in TNBC. There is currently no approved standard of care for people with previously-treated mTNBC.

About ASCENT

The international, open-label confirmatory Phase 3 study enrolled more than 500 patients with metastatic triple-negative breast cancer who had received at least two prior therapies for metastatic disease. Patients were randomized to receive either Trodelvy or a physician’s choice of chemotherapy. The primary endpoint of the study was progression-free survival. Secondary endpoints include overall survival, objective response rate, duration of response, time to onset of response, and other measures of safety and tolerability. More information about ASCENT is available at http://clinicaltrials.gov/show/NCT02574455.

About TRODELVY

Trodelvy (sacituzumab govitecan-hziy) is the lead product and the most advanced program in Immunomedics’ unique antibody-drug conjugate (ADC) platform. Trodelvy is an ADC that is directed against Trop-2, a cell-surface protein expressed in many solid cancers. Trodelvy binds to Trop-2 and delivers the anti-cancer drug, SN-38, to kill cancer cells. Immunomedics has an extensive development program for Trodelvy, including multiple ongoing studies in triple-negative breast cancer, metastatic urothelial cancer, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer, and metastatic non-small cell lung cancer, either as a monotherapy or in combination with other agents. Visit https://www.trodelvy.com/ for more information.

About Immunomedics

Immunomedics is a leader in next-generation antibody-drug conjugate (ADC) technology, committed to help transform the lives of people with hard-to-treat cancers. Our proprietary ADC platform centers on using a novel linker that does not require an enzyme to release the payload to deliver an active drug inside the tumor cell and the tumor microenvironment, thereby producing a bystander effect. Trodelvy, our lead ADC, is the first ADC the FDA has approved for the treatment of people with metastatic triple-negative breast cancer and is also the first FDA-approved anti-Trop-2 ADC. For additional information on the Company, please visit its website at https://immunomedics.com/. The information on its website does not, however, form a part of this press release.

Cautionary note regarding forward-looking statements

This release, in addition to historical information, may contain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding expectations for achieving full FDA approval based on our confirmatory data for TRODELVY and the Company’s development of TRODELVY for additional indications, clinical trials (including the funding therefor, anticipated patient enrollment, trial outcomes, timing or associated costs), regulatory applications and related timelines, including the filing and approval timelines for BLAs and BLA supplements, out-licensing arrangements, forecasts of future operating results, potential collaborations, capital raising activities, and the timing for bringing any product candidate to market, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, the Company’s reliance on third-party relationships and outsourcing arrangements (for example in connection with manufacturing, logistics and distribution, and sales and marketing) over which it may not always have full control, including the failure of third parties on which the Company is dependent to meet the Company’s business and operational needs for investigational or commercial products and, or to comply with the Company’s agreements or laws and regulations that impact the Company’s business; the Company’s ability to meet post-approval compliance obligations (on topics including but not limited to product quality, product distribution and supply chain requirements, and promotional and marketing compliance); imposition of significant post-approval regulatory requirements on our products, including a requirement for a post-approval confirmatory clinical study, or failure to maintain or obtain full regulatory approval for the Company’s products, if received, due to a failure to satisfy post-approval regulatory requirements, such as the submission of sufficient data from a confirmatory clinical study; the uncertainties inherent in research and development; safety and efficacy concerns related to the Company’s products and product candidates; uncertainties in the rate and degree of market acceptance of products and product candidates, if approved; inability to create an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure for distribution of the Company’s products and product candidates, if approved; inaccuracies in the Company’s estimates of the size of the potential markets for the Company’s products and product candidates or limitations by regulators on the proposed treatment population for the Company’s products and product candidates; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of the Company’s products and product candidates; the Company’s dependence on business collaborations or availability of required financing from capital markets, or other sources on acceptable terms, if at all, in order to further develop our products and finance our operations; new product development (including clinical trials outcome and regulatory requirements/actions); the risk that we or any of our collaborators may be unable to secure regulatory approval of and market our drug candidates; risks relating to the COVID-19 pandemic in the U.S. and around the world; risks associated with litigation to which the Company is or may become a party, including the cost and potential reputational damage resulting from such litigation; loss of key personnel; competitive risks to marketed products; and the Company’s ability to repay its outstanding indebtedness, if and when required, as well as the risks discussed in the Company’s filings with the Securities and Exchange Commission. The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.

Reference

1.  TRODELVY Prescribing Information. Morris Plains, NJ: Immunomedics Inc, 2020.

For More Information:

Dr. Chau Cheng
(862) 260-3727
ccheng@immunomedics.com

For Media Inquiries:

Darren Opland, Ph.D.
(646) 627-8387
Darren@lifescipublicrelations.com

Novartis Piqray® data show survival benefit for patients with HR+/HER2- advanced breast cancer with a PIK3CA mutation

  • In SOLAR-1 final analysis, Piqray (alpelisib) plus fulvestrant demonstrated 8 months clinically relevant improvement in overall survival (OS) in HR+/HER2- advanced breast cancer (aBC) patients with a PIK3CA mutation compared to fulvestrant alone1
     
  • 14+ months OS improvement was achieved in patients with lung or liver metastases, which are observed in 41% of postmenopausal women with HR+ aBC, and considered more aggressive and challenging to treat1-3 
     
  • Data add to growing body of evidence for Piqray, the first and only treatment specifically approved for aBC with a PIK3CA mutation 

Basel, September 19, 2020 — Novartis today announced results of the final overall survival (OS) analysis from the SOLAR-1 trial, which evaluated Piqray® (alpelisib) in combination with fulvestrant, compared to fulvestrant alone, in hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer patients with tumors harboring a PIK3CA mutation. Piqray is the only treatment approved in Europe, the United States and 15 other countries specifically for people with HR+/HER2- advanced breast cancer with a PIK3CA mutation. These data will be presented as a late-breaking oral presentation during the ESMO Virtual Congress 2020.

In the study, there was a clinically relevant improvement in OS of eight months for patients with a PIK3CA mutation taking Piqray plus fulvestrant compared to fulvestrant alone (median OS 39.3 months vs. 31.4 months; one-sided p≤0.0161; HR=0.86; 95% CI: 0.64-1.15; p=0.15)1. This difference did not reach the prespecified threshold of statistical significance set for the secondary objective of OS in patients with PIK3CA-mutated breast cancer. A more than 14 month OS improvement was observed in patients with lung or liver metastases, which signify more aggressive disease (median OS 37.2 months vs. 22.8 months; HR=0.68; 95% CI: 0.46-1.00)1-3.

“These results build on previous data showing that alpelisib nearly doubled median progression-free survival in this patient population,” said Fabrice André, MD, PhD, research director and head of INSERM Unit U981, professor in the Department of Medical Oncology at Institut Gustave Roussy in Villejuif, France, and global SOLAR-1 principal investigator. “Patients whose tumors have a PIK3CA mutation, particularly those with lung or liver metastases, have a more aggressive, harder to treat cancer, so these results showing alpelisib offers longer life, are promising.”
In addition, data showed the need for chemotherapy was delayed in patients taking Piqray plus fulvestrant by nine months compared to those taking fulvestrant alone (23.3 months vs. 14.8 months; HR=0.72; 95% CI: 0.54-0.95)1. Quality of life (QOL) was maintained for people taking Piqray plus fulvestrant.

“These data demonstrating survival benefit give the 40% of HR+/HER2- advanced breast cancer patients with PIK3CA mutations in their tumors more time to spend with loved ones and do what they value most,” said Susanne Schaffert, PhD, President, Novartis Oncology. “We are committed to reimagining a world where advanced breast cancer becomes a curable disease, and these data reinforce our confidence as we continue to explore the potential use of Piqray in other types of breast cancer with PIK3CA mutations.”

No new safety signals were observed; adverse events were consistent with previously reported SOLAR-1 results.

Visit https://www.virtualcongress.novartis.com/ESMO20 for the latest information from Novartis including our bold approach to reimagining cancer care, and access to our ESMO Virtual Congress 2020 symposia and data presentations (for registered participants).

In July 2020, the European Commission (EC) approved Piqray in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2- locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy.

About Piqray® (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen. Piqray is approved in 48 countries, including the US and European member states.

About SOLAR-1
SOLAR-1 is a global, Phase III, randomized, double-blind, placebo-controlled trial studying Piqray in combination with fulvestrant for postmenopausal women, and men, with PIK3CA-mutated HR+/HER2- advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor7-9.

The trial randomized 572 patients. Patients were allocated based on central tumor tissue assessment to either a PIK3CA-mutated cohort (n=341) or a PIK3CA non-mutated cohort (n=231). Within each cohort, patients were randomized in a 1:1 ratio to receive continuous oral treatment with Piqray (300 mg once daily) plus fulvestrant (500 mg every 28 days + Cycle 1 Day 15) or placebo plus fulvestrant. Stratification was based on visceral metastases and prior CDK4/6 inhibitor treatment7-9. Patients and investigators are blinded to PIK3CA mutation status and treatment.

The primary endpoint is local investigator assessed PFS using RECIST 1.1 for patients with a PIK3CA mutation. The key secondary endpoint is overall survival, and additional secondary endpoints include, but are not limited to, overall response rate, clinical benefit rate, health-related quality of life, efficacy in PIK3CA non-mutated cohort, safety and tolerability7-9.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.

Important Safety Information from the PIQRAY EU SmPC
The most common ADRs and the most common grade 3 / 4 ADRs (reported at a frequency >20% and ≥2%, respectively) were plasma glucose increased, creatinine increased, gamma-glutamyltransferase increased, rash, lymphocyte count decreased, nausea, alanine aminotransferase increased, anaemia, fatigue, lipase increased, decreased appetite*, stomatitis, vomiting*, weight decreased, hypocalcaemia, plasma glucose decreased*, activated partial thromboplastin time prolonged*, alopecia**, diarrhoea, hypokalaemia, hypertension, nausea, creatinine increased, and mucosal inflammation (*<2% grade 3/4 ADRs reported, ** no grade 3/4 ADRs reported).

Piqray can cause serious side effects such as severe hypersensitivity, severe cutaneous reactions, hyperglycaemia, pneumonitis, diarrhoea and osteonecrosis of the jaw.

The following should be taken into consideration prior to or during treatment with Piqray: 

Piqray should be permanently discontinued in patients with serious hypersensitivity reactions.

Piqray should not be initiated in patients with a history of severe cutaneous reactions, should be interrupted if signs or symptoms of severe cutaneous reactions are present, and permanently discontinued if a severe cutaneous reaction is confirmed.

Fasting glucose and HbA1c levels should be monitored frequently in the first 4 weeks of treatment, and patients should be advised of the signs and symptoms of hyperglycaemia.

In case of new or worsening respiratory symptoms, the patient should be evaluated for pneumonitis.

Patients should be advised to notify their physician if diarrhoea occurs.

Caution should be exercised when Piqray and bisphosphonates or denosumab are used together or sequentially. Piqray should not be initiated in patients with ongoing osteonecrosis of the jaw.

The efficacy and safety of Piqray has not been studied in patients with symptomatic visceral disease.

Animal studies suggest that Piqray may cause fetal harm in pregnant women. Therefore, as a precaution, women of childbearing potential should use effective contraception while receiving Piqray during treatment and at least 1 week after stopping treatment. Women should not breast feed for at least 1 week after the last dose of Piqray. Piqray may affect fertility in males and females.

Please see full Prescribing Information for Piqray, available at www.Piqray.com.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 140 nationalities work at Novartis around the world. Find out more at
https://www.novartis.com.

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References
1.    André F, Ciruelos EM, Juric D, et al. Overall Survival (OS) Results From SOLAR-1, a Phase 3 Study of Alpelisib (ALP) + Fulvestrant (FUL) for Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2–) Advanced Breast Cancer (ABC). Presented at the European Society for Medical Oncology (ESMO) Congress, September 19, 2020 (LBA18).   
2.    Harb, WA. Management of patients with hormone receptor-positive breast cancer with visceral disease: challenges and treatment options. Cancer Manag Res. 2015;7:37-46.
3.    Wang R, Zhu Y, Liu X, et al. The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer. 2019;19(1):1091.
4.    The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70.
5.    Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 2011.
6.    Saal LH, Johansson P, Holm K, et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci U S A. 2007;104(18):7564-7569.
7.    Piqray (alpelisib) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; May 2019.
8.    André F, Ciruelos E, Rubovszky G. Alpelisib for PIK3CA-Mutated, Hormone-Receptor-Positive Advanced Breast Cancer. N Eng J Med. 2019.
9.    André F, Ciruelos EM, Rubovszky G et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): Results of the phase III SOLAR-1 trial. Annals of Oncology, Vol 29, Suppl 8, October 2018, Abstract LBA3_PR.

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Novartis Media Relations
E-mail: media.relations@novartis.com

Anja von Treskow
Novartis External Communications
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anja.von_treskow@novartis.com

 

Eric Althoff
Novartis US External Communications
+1 646 438 4335
eric.althoff@novartis.com

Julie Masow
Novartis Oncology Media Relations
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julie.masow@novartis.com

 

Novartis Investor Relations
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Roche presents new data from multiple Phase III studies of Tecentriq in triple-negative breast cancer at ESMO Virtual Congress 2020

  • Data from the Phase III IMpassion031 study demonstrated that Tecentriq in combination with chemotherapy improved pathological complete response for patients with early triple-negative breast cancer (TNBC), when compared to placebo plus chemotherapy
  • Final overall survival data from the Phase III IMpassion130 study were consistent with prior interim analyses in patients with metastatic TNBC, whose tumours expressed PD-L1 and who received Tecentriq plus nab-paclitaxel
  • Results from the Phase III IMpassion131 study, evaluating Tecentriq in combination with paclitaxel for the treatment of people with metastatic TNBC and whose tumours expressed PD-L1, did not meet its primary endpoint of progression-free survival

Basel, 19 September 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that it presented the latest results from three Phase III studies from the Tecentriq® (atezolizumab) clinical development programme in triple-negative breast cancer (TNBC) at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“While we have made great progress in the treatment of many forms of breast cancer, TNBC remains an aggressive and difficult-to-treat disease,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are proud of our work to address challenges and advance scientific understanding of cancer immunotherapy in the context of distinct chemotherapy regimens and in various TNBC treatment settings. Although the IMpassion131 study did not reach its endpoint, we are pleased to bring new treatment options for some TNBC patients, and remain committed to improving the lives of all women with early and advanced stages of this disease.”

Results from the Phase III IMpassion031 study, evaluating Tecentriq in combination with chemotherapy (Abraxane®, albumin-bound paclitaxel; nab-paclitaxel; followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy (including nab-paclitaxel), demonstrated a statistically significant and clinically meaningful improvement in pathological complete response (pCR) for the treatment of people with early TNBC, regardless of PD-L1 expression. pCR was observed in 57.6% (95% CI: 49.7–65.2) of patients treated with Tecentriq in combination with chemotherapy, an increase of 16.5% from 41.1% (95% CI: 33.6–48.9) in patients treated with placebo plus chemotherapy (one-sided p=0.0044, significance boundary = 0.0184) in the intention-to-treat (ITT) population. The safety profile was consistent with the established profile of the individual drugs and no new safety concerns were identified.

The IMpassion031 study is the second positive Phase III study from Roche demonstrating the benefit of Tecentriq in TNBC, and the first Tecentriq study to demonstrate benefit in early TNBC. Tecentriq in combination with nab-paclitaxel is currently approved in more than 70 countries worldwide, including the US and across Europe, for the treatment of adults with unresectable locally advanced or metastatic TNBC in people whose tumours express PD-L1 (IC≥1%).

The final overall survival (OS) analysis of the Phase III IMpassion130 study, evaluating Tecentriq in combination with nab-paclitaxel, compared with placebo plus nab-paclitaxel, as a first-line treatment for patients with metastatic TNBC, was consistent with the first and second interim analyses. There was no significant difference in OS between the treatment groups in the ITT population. Clinically meaningful improvements in OS were seen with Tecentriq plus nab-paclitaxel in PD-L1-positive patients. The magnitude of OS improvements with Tecentriq in PD-L1-positive patients remained clinically meaningful, with an increase of 7.5 months in median OS with Tecentriq plus nab-paclitaxel, compared with placebo plus nab-paclitaxel (hazard ratio [HR]=0.67; 95% CI: 0.53–0.86). However, this result could not be formally tested due to the prespecified statistical testing hierarchy. The cumulative safety of the Tecentriq plus nab-paclitaxel combination remains consistent with the previously reported safety data for this study and the known risks of individual study drugs. No new safety concerns were identified with longer follow-up.

Finally, results from the Phase III IMpassion131 study, evaluating Tecentriq in combination with paclitaxel, compared with placebo plus paclitaxel, as a first-line treatment for patients with metastatic TNBC, did not show significant improvement for progression-free survival in the PD-L1-positive population (HR=0.82; 95% CI: 0.60–1.12). The OS data showed a negative trend; however, the study was not powered for the secondary endpoint of OS, and OS data were immature at time of analysis (initial HR=1.55 [95% CI: 0.86-2.80] in the PD-L1 positive population, based on 21% of patients with an event; updated HR=1.12 [95% CI: 0.76-1.65]), updated analysis based on 41% of patients with an event). The safety profile of Tecentriq plus paclitaxel was consistent with the established safety profile of the individual study drugs and no new safety concerns were identified.

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMpassion031 study
The IMpassion031 study is a Phase III, multicentre, randomised, double-blind study evaluating the efficacy and safety of Tecentriq (atezolizumab) in combination with chemotherapy (Abraxane®, albumin-bound paclitaxel; nab-paclitaxel; followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy, in people with previously untreated, early TNBC. The study enrolled 333 people who were randomised in a 1:1 ratio to receive Tecentriq or placebo plus chemotherapy in the neoadjuvant (before surgery) setting. Treatment with Tecentriq continued adjuvantly (after surgery) for those in the Tecentriq arm of the study. The primary endpoint is pCR using the American Joint Committee on Cancer (AJCC) staging system in the ITT population and in the PD-L1-positive population. Secondary endpoints include OS, event-free survival, disease-free survival and quality of life measures.

About the IMpassion130 study
The IMpassion130 study is a Phase III, multicentre, randomised, double-blind study evaluating the efficacy, safety, and pharmacokinetics of Tecentriq plus nab-paclitaxel compared with placebo plus nab-paclitaxel in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer (mBC). The study enrolled 902 people who were randomised equally (1:1). The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) and OS in the ITT population and in the PD-L1-positive population. Secondary endpoints include objective response rate and duration of response.

About the IMpassion131 study
The IMpassion131 study is a Phase III, multicentre, randomised, double-blind study evaluating the efficacy and safety of Tecentriq in combination with paclitaxel, in comparison to placebo plus paclitaxel, in people with previously untreated, inoperable, locally advanced or metastatic TNBC. The study enrolled 651 people who were randomised in a 2:1 ratio to receive Tecentriq or placebo plus paclitaxel. The primary endpoint is PFS per investigator assessment (RECIST 1.1) in the PD-L1-positive population followed by ITT populations. Secondary endpoints include OS, ORR and duration of response in the PD-L1-positive and ITT populations.

About triple-negative breast cancer
Breast cancer is the most common cancer among women with more than 2 million diagnosed worldwide each year.1 TNBC represents ~15% of all breast cancers and is more common in women under the age of 50, compared with other forms of breast cancer.2-4 It is defined by the lack of expression and/or amplification of the targetable receptors for oestrogen, progesterone and HER2 amplification.5 Patients with metastatic TNBC generally experience rapid progression and shorter OS compared to other subtypes of breast cancer.3

About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough innovations in HER2-positive and triple negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for all forms of early and advanced breast cancer, including triple-negative and hormone receptor-positive.

Our targeted medicines Herceptin, Perjeta, Kadcyla and Tecentriq are continuing to transform the treatment of early and advanced HER2-positive and triple negative breast cancers and, through our Tecentriq and ipatasertib clinical programmes, we hope to bring new treatment combinations to people with breast cancer, ultimately improving outcomes.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer and in PD-L1-positive metastatic triple-negative breast cancer. In the US, Tecentriq in combination with Avastin is approved for people with unresectable or metastatic HCC.

About Roche in cancer immunotherapy
Roche’s rigorous pursuit of groundbreaking science has contributed to major therapeutic and diagnostic advances in oncology over the last 50 years, and today, realising the full potential of cancer immunotherapy is a major area of focus. With over 20 molecules in development, Roche is investigating the potential benefits of immunotherapy alone, and in combination with chemotherapy, targeted therapies or other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system to attack their cancer. Our scientific expertise, coupled with innovative pipeline and extensive partnerships, gives us the confidence to continue pursuing the vision of finding a cure for cancer by ensuring the right treatment for the right patient at the right time.

In addition to Roche’s approved PD-L1 checkpoint inhibitor, Tecentriq® (atezolizumab), Roche’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, such as tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, individualised neoantigen therapies and T-cell bispecific antibodies. To learn more about Roche’s scientific-led approach to cancer immunotherapy, please follow this link:
http://www.roche.com/research_and_development/what_we_are_working_on/oncology/cancer-immunotherapy.htm

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
[1]World Health Organization: Globocan 2018 – Breast Cancer Factsheet. [Internet; cited 24 July] Available from: http://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf.
[2] Yao H et al. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget. 2017;8(1):1913–1924.
[3] BreastCancer.org. What is Triple-Negative Breast Cancer? [Internet; cited 24 July] Available from: https://www.breastcancer.org/symptoms/diagnosis/trip_neg?what.
[4] Cancer Treatment Centers of America. Triple negative breast cancer risk factors. [Internet; cited 24 July] Available from: https://www.cancercenter.com/breast-cancer/risk-factors/tab/triple-negative-breast-cancer-risk-factors/.
[5] Pal SK et al. Triple negative breast cancer: unmet medical needs. Breast Cancer Res Treat. 2011;125(3):627–636.

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Novartis reports late-breaking data from Phase III COMBI-i trial of spartalizumab (PDR001) with Tafinlar® and Mekinist® in advanced melanoma

  • Based on unprecedented progression-free survival results, Tafinlar (dabrafenib) + Mekinist (trametinib) confirmed as standard-of-care, targeted therapy for advanced BRAF-mutated melanoma1-4
     
  • Data show positive durable responses and progression-free survival benefit for patients treated with Tafinlar + Mekinist in the comparator arm of the COMBI-i clinical trial despite the study not meeting the primary endpoint for the investigational triplet therapy
     
  • Spartalizumab development program continues, investigating the immunotherapy in combination with other anti-cancer agents

Basel, September 19, 2020 — Novartis announced today detailed results from the Phase III COMBI-i trial evaluating the investigational immunotherapy spartalizumab (PDR001) in combination with the targeted therapies Tafinlar® (dabrafenib) and Mekinist® (trametinib) compared to Tafinlar + Mekinist alone1. The efficacy data achieved in the trial’s control arm among patients treated with Tafinlar + Mekinist represent the longest progression-free survival results (PFS) observed across multiple Phase III studies. The trial did not meet its primary endpoint of investigator-assessed progression-free survival (PFS) for patients treated with the investigational triplet therapy1-4

The COMBI-i study was conducted among treatment-naive patients with advanced BRAF V600 mutation-positive cutaneous melanoma. Results were presented today as a late-breaking oral presentation during the European Society of Medical Oncology (ESMO) Virtual Congress 20201.

“For treating physicians and patients alike, the durable, progression-free survival seen with dabrafenib + trametinib in COMBI-i confirms that this targeted therapy combination remains a gold standard treatment for people with advanced BRAF-mutated melanoma,” said Dr. Paul Nathan, consultant medical oncologist, Mount Vernon Cancer Centre, United Kingdom, and COMBI-i principal investigator. “The good news is that the control arm of the study performed better than we originally expected, with the efficacy of dabrafenib + trametinib improving consistently over time. Although the study did not meet its primary endpoint, an important trend was seen in favor of the triple therapy arm. There is clearly more for us to learn about patients who may benefit from the potential addition of an immunotherapy.”

Findings from this randomized, double-blind, placebo-controlled study showed a median time of PFS of 16.2 months for patients treated with the triple therapy (n=267) compared to 12.0 months for patients receiving the combination Tafinlar + Mekinist alone (n=265; hazard ratio [HR] 0.82; 95% CI 0.655-1.027; p=0.042)1. Overall response rate was 68.5% for spartalizumab with Tafinlar + Mekinist (95% CI, 62.6-74.1%) compared to 64.2% for Tafinlar + Mekinist alone (95% CI, 58.1-69.9%)1. A significant duration of response (DOR) was seen in the study as median DOR for the triple therapy was not reached at two-year data cutoff, compared to 20.7 months with Tafinlar + Mekinist1.

“Working with our clinical investigator partners and melanoma patients around the world, we undertook the COMBI-i study to learn more about how we can continue to improve patient outcomes, and we are proud that it advanced the community’s scientific understanding about potential triplet therapies,” said Jeff Legos, Ph.D., MBA, Senior Vice President and Head of Oncology Drug Development. “The study results reinforce that patients taking Tafinlar + Mekinist continue to see durable responses and a meaningful progression-free survival benefit, consistent with data reported in previous Phase III studies.”

“As we continue to deliver Tafinlar + Mekinist to patients around the world, Novartis will continue to advance the science with bold investigations into uses for immunotherapy in cancer, including the ongoing development of spartalizumab, across a range of tumor types,” Legos added.

About the COMBI-i Study1
COMBI-i was a Phase III, double-blinded global study (NCT02967692) evaluating the investigational anti-PD1 therapy spartalizumab in combination with Tafinlar + Mekinist compared to Tafinlar + Mekinist and placebo as first-line therapy in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The study was conducted in three parts. In the safety run-in (part 1), the primary endpoint was incidence of dose-limiting toxicities, and in the biomarker cohort (part 2), the primary endpoint was immune microenvironment and biomarker modulation. In the randomized portion of the study (part 3), the primary endpoint was investigator-assessed progression-free survival.

COMBI-i study participants were classified as having either Stage IIIC (unresectable) or Stage IV (metastatic) disease and received study treatments as first-line therapy. No new side effects were seen and the safety profile in the control arm was consistent with what has been observed in previous studies. COMBI-i also evaluated a new side effect management protocol to address pyrexia – or fever – a common side effect seen among targeted therapies.

Serious treatment-related adverse events (TRAEs) grade ≥3 occurred in 23.2% of patients in the triple therapy arm compared to 11% in the Tafinlar + Mekinist arm. The most common grade ≥3 adverse events independent of treatment relationship observed in the triple therapy and Tafinlar + Mekinist arms were blood creatine phosphokinase increase (7.9% vs 7.2%), pyrexia (5.2% vs 3.0%), aspartate aminotransferase increase (3.7% vs 1.1%), fatigue (3.4% vs 1.9%), rash (3.4% vs 0.4%), asthenia (2.2% vs. 1.1%), headache (1.1% vs. 1.5%), diarrhea (0.7% vs. 1.9%), nausea (0.7% vs 0.4), arthralgia (0.7% vs 1.5%), and chills (zero vs. 0.8%). TRAEs leading to discontinuation of all 3 study drugs occurred in 12% compared to 8% of patients, respectively.

Visit https://www.virtualcongress.novartis.com/esmo20/ for the latest information from Novartis including our bold approach to reimagining cancer care, and access to our ESMO Virtual Congress 2020 symposia and data presentations (for registered participants).

About Spartalizumab (PDR001)
Spartalizumab is an investigational monoclonal antibody directed against the human programmed death-1 (PD-1) receptor. Its development program continues, investigating the immunotherapy across a range of tumor types.

About Tafinlar + Mekinist2-4
The combination of the targeted therapies Tafinlar + Mekinist, the worldwide leader in BRAF/MEK-inhibition, is approved for the treatment of patients with unresectable or metastatic BRAF-mutated melanoma by the US Food and Drug Administration (FDA) and European Commission based on data from the pivotal Phase III COMBI-d and COMBI-v trials.

In COMBI-d, Tafinlar + Mekinist achieved a statistically significant overall survival (OS) benefit compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months; Hazard Ratio [HR] 0.71 [95% Confidence Interval (CI), 0.55-0.92], p=0.01). The median progression-free survival (PFS) was 9.3 months in the 211 patients receiving combination therapy compared to 8.8 months in the 212 patients receiving monotherapy (HR 0.75 [95% CI, 0.57-0.99], p=0.035).

In COMBI-v, Tafinlar + Mekinist demonstrated a statistically significant OS benefit compared to vemurafenib monotherapy (median not reached vs 17.2 months; HR 0.69 [95% CI, 0.53-0.89], p=0.005). The median PFS was 11.4 months in the 352 patients receiving the Tafinlar + Mekinist combination compared to 7.3 months in the 352 patients receiving vemurafenib monotherapy (HR 0.56 [95% CI, 0.46-0.69], p<0.001).

Tafinlar + Mekinist Indication and Important Safety Information
Tafinlar and Mekinist are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

  • That has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
  • That has a certain type of abnormal “BRAF” (V600E or V600K mutation-positive) gene

Tafinlar and Mekinist are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal “BRAF” gene from coming back after the cancer has been removed by surgery.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal “BRAF V600E” gene.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

  • That has spread to other parts of the body and you have no satisfactory treatment options, and
  • That has a certain type of abnormal “BRAF” gene

Tafinlar, in combination with Mekinist, should not be used to treat people with wild-type BRAF melanoma. Mekinist should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that Tafinlar and Mekinist, in combination, are right for you.

It is not known if Tafinlar and Mekinist are safe and effective in children.

Tafinlar and Mekinist, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When Tafinlar is used in combination with Mekinist, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like “coffee grounds,” or red or black stools that look like tar.

Mekinist, alone or in combination with Tafinlar, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider immediately if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

Tafinlar, in combination with Mekinist, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of Tafinlar and Mekinist can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

Tafinlar, in combination with Mekinist, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

Tafinlar, in combination with Mekinist, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with Tafinlar in combination with Mekinist, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of Tafinlar in combination with Mekinist. In some cases, these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with Tafinlar in combination with Mekinist. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.
Tafinlar may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

Tafinlar, in combination with Mekinist, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with Tafinlar and Mekinist and for at least 4 months after the last dose of Tafinlar and Mekinist. For women of reproductive potential, Tafinlar and Mekinist, in combination, may harm your unborn baby. Use effective birth control (contraception) during treatment with Tafinlar and Mekinist in combination, and for 4 months after stopping treatment with Tafinlar and Mekinist. The most common side effects for patients with metastatic melanoma are: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma receiving the combination as adjuvant therapy are: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.

Please see full Prescribing Information for Tafinlar at https://www.novartis.us/sites/www.novartis.us/files/tafinlar.pdf
and Mekinist at https://www.novartis.us/sites/www.novartis.us/files/mekinist.pdf.

Disclaimer 
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis 
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.  

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References

  1. Nathan P, et al. Spartalizumab plus dabrafenib and trametinib in patients with previously untreated BRAF V600–mutant unresectable or metastatic melanoma: results from the randomized part 3 of the Phase III COMBI-i trial. Presentation Number LBA43. ESMO Virtual Congress 2020, September 19-21, 2020.
  2. Robert C, et al. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med. 2019 June 4. doi: 10.1056/NEJMoa1904059.
  3. TAFINLAR® (dabrafenib) Prescribing Information. Novartis Pharmaceuticals Corporation, April 2020. Available at: https://www.novartis.us/sites/www.novartis.us/files/tafinlar.pdf.
  4. MEKINIST® (trametinib) Prescribing Information. Novartis Pharmaceuticals Corporation, April 2020. Available at: https://www.novartis.us/sites/www.novartis.us/files/mekinist.pdf.