AstraZeneca furthers ambition to transform outcomes in early lung cancer and ​redefine metastatic breast cancer treatment at ASCO 2024​




AstraZeneca furthers ambition to transform outcomes in early lung cancer and ​redefine metastatic breast cancer treatment at ASCO 2024​

Back-to-back plenary presentations from LAURA and ADRIATIC Phase III trials reinforce the potential of TAGRISSO^® (osimertinib) and IMFINZI^® (durvalumab) in early lung cancer settings​

DESTINY-Breast06 data underscore potential of ENHERTU^® (fam-trastuzumab deruxtecan-nxki) earlier in HR-positive, HER2-low breast cancer treatment, and in a broader population including HER2-ultralow

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca advances its ambition to redefine cancer care with new data across its industry-leading portfolio and pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 31 to June 4, 2024.

More than 100 abstracts will feature 25 approved and potential new medicines across the Company’s diverse oncology portfolio and pipeline, including two late-breaking plenary presentations, a special late-breaking abstract session presentation and 15 oral presentations. Highlights include:

• LAURA Phase III trial of TAGRISSO^® (osimertinib) in unresectable, Stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT) (Plenary LBA4).
• ADRIATIC Phase III trial of IMFINZI^® (durvalumab) in patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed following concurrent CRT (cCRT) (Plenary LBA5).
• DESTINY-Breast06 Phase III trial of ENHERTU^® (fam-trastuzumab deruxtecan-nxki) in patients with metastatic hormone receptor (HR)-positive HER2-low and HER2-ultralow metastatic breast cancer following one or more lines of endocrine therapy (LBA1000).
• First-in-human, investigator-initiated trial of C-CAR031, a novel autologous armored Glypican 3 (GPC3) targeting chimeric antigen receptor T cell (CAR-T) therapy, in patients with liver cancer. The CAR-T is based on AZD5851, a novel cell therapy designed by AstraZeneca (Rapid Oral Abstract 4019).
• Two late-breaking presentations from the externally sponsored I-SPY2.2 Phase II trial of neoadjuvant datopotamab deruxtecan (Dato-DXd), alone and in combination with IMFINZI, in patients with breast cancer (LBA501 and LBA509).

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Our plenary data at ASCO show the pioneering role of our medicines in curative-intent lung cancer treatment and highlight progress toward our continued ambition to have a medicine for more than half of all patients treated for lung cancer by 2030. The overwhelming efficacy in the LAURA trial will add to the extensive body of evidence for TAGRISSO in EGFR-mutated non-small cell lung cancer, and the impressive survival data from ADRIATIC will show the potential of IMFINZI to transform outcomes in limited-stage small cell lung cancer.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Data from our antibody drug conjugates at ASCO underscore the opportunity to replace traditional chemotherapy with these medicines for many patients as we expand their use to new populations. DESTINY-Breast06 results will demonstrate the potential to treat patients across a broader spectrum of HR-positive metastatic breast cancer with ENHERTU, including those with HER2-ultralow expression who have never had access to HER2-directed therapy before. We’re also excited by the I-SPY2.2 efficacy and tolerability data for datopotamab deruxtecan plus IMFINZI, which will show the potential of combining antibody drug conjugates with immunotherapy in the early-stage setting.”

Transforming treatment expectations across earlier-stage lung cancer settings

Several presentations will reinforce the Company’s progress toward moving lung cancer treatment to earlier stages of disease. These include:

• A late-breaking plenary presentation showcasing progression-free survival (PFS) results from the LAURA Phase III trial evaluating TAGRISSO in unresectable, Stage III EGFRm NSCLC after CRT. In February, high-level results showed a statistically significant and highly clinically meaningful PFS benefit for TAGRISSO in this setting.
• A late-breaking plenary presentation highlighting overall survival (OS) and PFS results from the ADRIATIC Phase III trial of IMFINZI in patients with LS-SCLC who had not progressed following cCRT. In April, high-level results from an interim analysis showed a statistically significant and clinically meaningful OS and PFS benefit for IMFINZI in this setting.
• An oral presentation of an analysis from the ADAURA Phase III trial of TAGRISSO in the adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC, assessing the potential for circulating tumor DNA-based molecular residual disease to predict disease recurrence.
• A rapid oral presentation of an exploratory analysis from the AEGEAN Phase III trial of IMFINZI-based treatment before and after surgery in patients with resectable early-stage (IIA-IIIB) NSCLC, evaluating efficacy in patients with N2 disease (cancer in the lymph nodes on the same side as the affected lung or between the lungs).
• A poster presentation of updated OS, PFS and safety results from the COAST Phase II trial of IMFINZI in combination with novel immunotherapies oleclumab, an anti-CD73 monoclonal antibody, and monalizumab, an anti-NKG2A monoclonal antibody, in unresectable, Stage III NSCLC, supporting the PACIFIC-9 Phase III trial in this patient population.

In metastatic lung cancer, the Company will present data that underscore its commitment to extending the benefits of antibody drug conjugates (ADCs) to more patients. A poster presentation will share updated safety and efficacy results, including PD-L1 expression, from the TROPION-Lung02 Phase Ib trial of datopotamab deruxtecan plus pembrolizumab with or without platinum chemotherapy as 1st-line treatment for patients with advanced NSCLC without actionable genomic alterations. These data build on previously presented results from the TROPION-Lung-1 Phase III trial demonstrating the potential of this novel ADC in advanced disease. Datopotamab deruxtecan in combination with immunotherapies is being further explored in multiple Phase III trials in this setting, including AVANZAR, TROPION-Lung07 and TROPION-Lung08.

Redefining the breast cancer treatment landscape with ADCs across subtypes and stages of disease

A late-breaking presentation will showcase efficacy and safety outcomes from the DESTINY-Breast06 Phase III trial. In April, high-level results showed ENHERTU demonstrated a statistically significant and clinically meaningful improvement in PFS versus standard-of-care chemotherapy in patients with HR-positive, HER2-low metastatic breast cancer. A clinically meaningful PFS improvement was also seen in patients with HER2-ultralow expression.

An oral presentation will spotlight data from an interim analysis of the dose-expansion phase of the DESTINY-Breast07 Phase 1b/II trial assessing ENHERTU alone or in combination with pertuzumab as 1st-line treatment in HER2-positive metastatic breast cancer. These regimens are being further explored in the DESTINY-Breast09 Phase III clinical trial.

Additionally, a poster presentation will share updated OS and PFS results from the DESTINY-Breast03 Phase III trial of ENHERTU versus trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.

An oral presentation will feature patient-reported outcomes data from the TROPION-Breast01 Phase III trial of datopotamab deruxtecan in patients with inoperable or metastatic HR-positive, HER2-low or negative breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. Previously presented primary results from TROPION-Breast01 showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS versus investigator’s choice of chemotherapy.

Two late-breaking presentations of results from the externally sponsored I-SPY2.2 Phase II trial will highlight the rates of pathological complete response associated with neoadjuvant datopotamab deruxtecan, alone and in combination with IMFINZI, across breast cancer subtypes.

Advancing the next wave of medicines and combination therapies to attack cancer from multiple angles

A rapid oral presentation will spotlight safety and preliminary efficacy results from an investigator-initiated Trial of C-CAR031, a novel autologous armored Glypican 3 (GPC3) targeting chimeric antigen receptor T cell (CAR-T) therapy that is being investigated for hepatocellular carcinoma. The CAR-T is based on AZD5851, a novel cell therapy designed by AstraZeneca using their transforming growth factor-beta receptor II (TGFβRII) dominant negative armoring platform and is manufactured by AbelZeta Pharmaceuticals Inc. C-CAR031 is being developed in China under a co-development agreement between AbelZeta and AstraZeneca. AstraZeneca’s TGFβRII dominant negative armoring is designed to resist the immuno-suppressive tumor microenvironment and enhance the potential effectiveness of CAR-Ts in solid tumors.

A rapid abstract update will feature updated efficacy data from a Phase I trial of AZD0901, a potential first-in-class ADC targeting Claudin 18.2, which has shown promise as a therapeutic target in gastric cancer. First results were presented at the ASCO Plenary Series 2023.

Additionally, a clinical science symposium presentation of the externally sponsored CAPRI Phase II trial will share efficacy and safety results for ceralasertib, an ataxia telangiectasia and rad3-related (ATR) kinase inhibitor, plus LYNPARZA (olaparib) in patients with platinum-sensitive recurrent high-grade serious ovarian cancer.

Collaboration in the scientific community is critical to improving outcomes for patients. AstraZeneca is collaborating with Daiichi Sankyo Company Limited to develop and commercialize ENHERTU and datopotamab deruxtecan, and with Merck & Co., Inc. (MSD outside of the US and Canada) to develop and commercialize LYNPARZA. AstraZeneca obtained full oncology rights to monalizumab from Innate Pharma in October 2018 through a co-development and commercialization agreement initiated in 2015.

Key AstraZeneca presentations during ASCO 2024

IMPORTANT SAFETY INFORMATION FOR TAGRISSO^® (osimetinib)

• There are no contraindications for TAGRISSO
• Interstitial lung disease (ILD)/pneumonitis occurred in 4% of the 1813 TAGRISSO-treated patients; 0.4% of cases were fatal. In the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 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/pneumonitis is confirmed
• Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% 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 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to less than 50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. 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 0.6% of 1813 patients treated with TAGRISSO monotherapy 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 erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed
• Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
• Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.06% of 1813) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
• 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
• Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the final dose
• Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
  • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
  • TAGRISSO in combination with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine

INDICATIONS

• TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with 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 first-line treatme

Contacts

Media Inquiries

Brendan McEvoy, +1 302 885 2677

Chelsea Tressler, +1 302 885 2677

US Media Mailbox: usmediateam@astrazeneca.com

Read full story here