AstraZeneca Data at WCLC Advance Ambition to Have an AstraZeneca Medicine for More Than Half of All Patients Treated for Lung Cancer by 2030
AstraZeneca Data at WCLC Advance Ambition to Have an AstraZeneca Medicine for More Than Half of All Patients Treated for Lung Cancer by 2030
FLAURA2 data reinforce TAGRISSO® as backbone therapy for EGFR-mutated advanced lung cancer in combination with chemotherapy; granted Breakthrough Therapy Designation in the US
Further results for ENHERTU®, IMFINZI® and datopotamab deruxtecan showcase strength of diverse ADC and IO portfolios to address unmet needs
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca advances its robust lung cancer portfolio and pipeline at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC), September 9-12, 2023.
More than 40 abstracts will feature eight approved and potential new medicines from AstraZeneca, including nine oral presentations and a late-breaking plenary Presidential Symposium presentation of results from the FLAURA2 Phase III trial of TAGRISSO® (osimertinib) in combination with chemotherapy for patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) lung cancer.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Our data at WCLC support our ambition to have the right AstraZeneca medicine for more than half of all patients treated for lung cancer by 2030, and underscore the need to increase screening and early diagnosis to improve patient outcomes. The strong results from FLAURA2 will further establish TAGRISSO as the backbone therapy in EGFR-mutated non-small cell lung cancer, and the recent Breakthrough Therapy Designation in the US is a significant validation of the potential we see for this regimen.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Following last year’s accelerated approval of ENHERTU as the first HER2-directed therapy for patients with previously treated HER2-mutant metastatic lung cancer, new data at WCLC will reinforce its potential benefit to patients in need of targeted options. In addition, data for datopotamab deruxtecan will further support the potential to combine this agent with immune checkpoint inhibitors and the continued investigation of these combinations in first-line settings.”
Improving outcomes across early- and late-stage EGFRm lung cancer
A late-breaking plenary Presidential Symposium presentation will showcase progression-free survival (PFS) data from the FLAURA2 Phase III trial evaluating TAGRISSO in combination with chemotherapy for patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm non-small cell lung cancer (NSCLC). In May, high-level results showed the TAGRISSO combination demonstrated a statistically significant and clinically meaningful improvement in PFS compared to standard-of-care TAGRISSO monotherapy. In August, TAGRISSO plus chemotherapy was granted Breakthrough Therapy Designation in the US for advanced EGFRm NSCLC.
An oral presentation of results from a Phase IIIb trial will show the potential of savolitinib as a 1st-line treatment for advanced or metastatic NSCLC harboring MET exon 14 mutations. Savolitinib is approved for this indication in China.
In addition, an e-poster on a computational pathology analysis of MET expression in patients treated with a combination of savolitinib and TAGRISSO in the SAVANNAH Phase II trial will showcase the Company’s progress in developing transformational technology solutions to identify patients who are most likely to respond to treatment. Encouraging efficacy for the combination has been previously reported in the same study in patients with high levels of MET overexpression and/or amplification whose disease progressed on treatment with TAGRISSO.
Realizing the potential of antibody drug conjugates (ADCs) in advanced lung cancer
A late-breaking oral presentation of first results from the TROPION-Lung04 Phase Ib trial will highlight the safety and efficacy of datopotamab deruxtecan (Dato-DXd) plus IMFINZI® (durvalumab) with and without carboplatin in patients with previously treated or untreated, advanced or metastatic NSCLC without actionable genomic alterations. There are currently no TROP2-directed ADCs approved for the treatment of patients with lung cancer.
A mini-oral presentation of primary results from the DESTINY-Lung02 Phase II trial will share the first overall survival and PFS data for ENHERTU® (fam-trastuzumab deruxtecan-nxki) in patients with previously treated HER2-mutant metastatic NSCLC. ENHERTU is approved for this indication in a number of countries, including in the US, where it was granted accelerated approval based on interim results from the trial.
Two posters will feature AZD9592, an EGFR/cMET bispecific ADC designed to deliver targeted chemotherapy to cancer cells expressing both EGFR and cMET with a topoisomerase inhibitor 1 warhead using the Company’s proprietary linker technology. A trial-in-progress poster will describe the EGRET Phase I trial, a first-in-human study evaluating AZD9592 in patients with advanced solid tumors including in combination with TAGRISSO in metastatic EGFRm NSCLC. In addition, a poster on translational results for AZD9592 suggests it may provide clinical benefit in areas of unmet need, including in patients with NSCLC previously treated with chemotherapy or targeted agents. This is the Company’s first bispecific ADC to enter the clinic.
Reinforcing IMFINZI benefits alone and in novel combinations across lung cancer settings
Two late-breaking oral presentations will share new data from the AEGEAN Phase III trial of IMFINZI in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery in patients with resectable NSCLC, including key surgical outcomes and exploratory analyses of clinical outcomes in a subset of patients with EGFRm disease. Previously presented primary results from AEGEAN demonstrated statistically significant and clinically meaningful improvement in event-free survival and pathologic complete response with this IMFINZI-based regimen versus neoadjuvant chemotherapy alone followed by surgery.
Another oral presentation of data from a planned subset analysis of the PACIFIC-R observational study of IMFINZI in a real-world population of patients with EGFRm disease will explore the long-term clinical outcomes of IMFINZI in patients with unresectable, Stage III NSCLC.
Data will also be shared from new exploratory subgroup analyses of the POSEIDON Phase III trial describing patients deriving long-term benefit from the combination of IMFINZI, IMJUDO® (tremelimumab-actl) and chemotherapy in the metastatic NSCLC setting.
Advancing our commitment to increase lung cancer screening and early diagnosis
An oral presentation will describe a framework to support government implementation of high-quality and impactful lung cancer screening programs. Screening is essential to early detection and reducing lung cancer mortality. Published in March 2023, the framework was developed by the Lung Cancer Policy Network, an initiative of the Lung Ambition Alliance aimed at elevating lung cancer as a policy priority worldwide. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.
Collaboration in the scientific community is critical to improving outcomes for patients. AstraZeneca is collaborating with Daiichi Sankyo to develop and commercialize ENHERTU and datopotamab deruxtecan, and with HUTCHMED to develop and commercialize savolitinib.
Key AstraZeneca presentations during WCLC 2023
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Lead Author |
Abstract Title |
Presentation details (SGT) |
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Tumor drivers and resistance |
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Janne, PA |
Osimertinib With/Without Platinum-Based Chemotherapy as First-line Treatment in Patients with EGFRm Advanced NSCLC (FLAURA2)
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Abstract #PL03.13 Plenary Session 3: Presidential Symposium 11 September 2023 9:40 AM |
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Lu, S |
A Phase 3b Study of 1L Savolitinib in Patients with Locally Advanced or Metastatic NSCLC Harboring MET Exon 14 Mutation
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Abstract #OA21.03 Oral Session MET Matters in NSCLC 12 September 2023 2:32 PM |
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Soo, R |
TARGET: A Phase II Study of 5-year Adjuvant Osimertinib in Completely Resected EGFR-mutated Stage II-IIIB NSCLC |
Abstract #P1.25-09 Poster Session Early-Stage Non-small Cell Lung Cancer 10 September 2023 5:30 PM |
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Tan, DSW |
OSTARA: A Phase II Study of First-line Osimertinib Combined with Amivantamab in EGFRm Advanced Non-Small Cell Lung Cancer |
Abstract #P2.09-17 Poster Session Metastatic Non-small Cell Lung Cancer – Targeted Therapy 11 September 2023 6:00 PM |
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Christ, S |
Computational Pathology-Based Assessment of cMET IHC Expression for Patient Selection in the Treatment of MET Overexpressing NSCLC |
Abstract #EP06.05-09 E-Poster Session Pathology and Biomarkers On-Demand |
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Antibody drug conjugates |
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Papadopoulos, KP
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Datopotamab Deruxtecan (Dato-DXd) + Durvalumab ± Carboplatin in Advanced/mNSCLC: Initial Results from Phase 1b TROPION-Lung04 |
Abstract #OA05.06 Oral Session Antibody Drug Conjugates: The Next Tsunami 10 September 2023 3:32 PM |
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Janne, P |
Trastuzumab Deruxtecan in Patients with HER2-Mutant Metastatic Non-Small Cell Lung Cancer: Primary Results of DESTINY-Lung02 |
Abstract #MA13.10 Mini Oral Session Targeted Therapy: EGFR and Her2 11 September 2023 4:25 PM |
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McGrath, L |
In Vivo Efficacy of AZD9592, an EGFR-cMET Bispecific ADC, in a Broad Panel of NSCLC Patient-Derived Xenograft Models |
Abstract #P1.12-04 Poster Session Tumor Biology – Translational Biology 10 September 2023 5:30 PM |
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Aggarwal, C |
AVANZAR: Phase III Study of Datopotamab Deruxtecan (Dato-DXd) + Durvalumab + Carboplatin as 1L Treatment of Advanced/mNSCLC |
Abstract #P2.04-02 Poster Session Metastatic Non-small Cell Lung Cancer – Cytotoxic Therapy 11 September 2023 6:00 PM |
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Aggarwal, C |
EGRET: First-in-human Study of the Novel Antibody-drug Conjugate AZD9592 ± Anti-cancer Agents in Advanced Solid Tumors |
Abstract #P2.04-03 Poster Session Metastatic Non-small Cell Lung Cancer – Cytotoxic Therapy 11 September 2023 6:00 PM |
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Zhou, C |
TROPION-Lung08: Datopotamab deruxtecan plus pembrolizumab in untreated advanced/metastatic non-small cell lung cancer (NSCLC) |
Abstract #P2.08-01 Poster Session Metastatic Non-small Cell Lung Cancer – Immunotherapy 11 September 2023 6:00 PM |
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Immuno-Oncology |
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Mitsudomi, T |
Surgical outcomes with neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in resectable NSCLC (AEGEAN) |
Abstract #OA12.05 Oral Session Pushing the Boundaries: Adjuvant and Neoadjuvant Approaches in Early Stage Non-small Cell Lung Cancer 11 September 2023 12:22 PM |
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He, J |
Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab in Resectable EGFR-mutated NSCLC (AEGEAN) |
Abstract #OA12.06 Oral Session Pushing the Boundaries: Adjuvant and Neoadjuvant Approaches in Early Stage Non-small Cell Lung Cancer 11 September 2023 12:32 PM |
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Peters, S |
Real-World Outcomes with Durvalumab After Chemoradiotherapy in Unresectable Stage III EGFR-Mutated NSCLC (PACIFIC-R) |
Abstract #OA17.03 Oral Session Next Steps in Locally Advanced NSCLC: Optimizing Techniques & Choosing Populations That Benefit 11 September 2023 3:47 PM |
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Cho, BC |
Durvalumab ± Tremelimumab + Chemotherapy in 1L Metastatic NSCLC: Characterisation of patients with PFS ≥12 months in POSEIDON |
Abstract #P2.06-05 Poster Session Metastatic Non-small Cell Lung Cancer – Immunotherapy 11 September 2023 6:00 PM |
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Advancing lung cancer screening |
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Lam, SC |
Taking A Health Systems Approach to Low-Dose CT Lung Cancer Screening: A Bespoke Framework to Support Implementation
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Abstract #OA16.03 Oral Session Expanding the Scope of Lung Cancer Screening Initiatives Worldwide 11 September 2023 3:47 PM |
SELECT SAFETY INFORMATION FOR TAGRISSO® (osimertinib)
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in patients treated with TAGRISSO, some of which were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening respiratory symptoms. Permanently discontinue if confirmed
- Monitor patients who have a history or predisposition for QTc prolongation or those who are taking medications that are 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 TAGRISSO-treated patients, some of which were fatal. Monitor patients with cardiac risk factors and assess left ventricular ejection fraction in patients who develop symptoms during treatment. Permanently discontinue TAGRISSO in patients with symptomatic congestive heart failure
- Promptly refer patients with signs and symptoms of keratitis to an ophthalmologist
- Withhold TAGRISSO if erythema multiforme major, Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected and permanently discontinue if confirmed
- 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, including fatal cases, has been reported in patients treated with TAGRISSO. Inform patients of the signs and symptoms of aplastic anemia. 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 women prior to use. Advise women to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise men to use effective contraception during treatment with TAGRISSO and for 4 months after the final dose
- Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough
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 treatment of adult 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 adult 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 for TAGRISSO.
IMPORTANT SAFETY INFORMATION FOR ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
-
Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
- Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
- Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen
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WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY |
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Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.
Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)
In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. Median time to first onset was 5 months (range: 0.9 to 23).
Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level.
Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)
In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Sixteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 664). Febrile neutropenia was reported in 1.1% of patients.
Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)
In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.6% of patients, of which 0.4% were Grade 3.
Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level.
Adverse Reactions
Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 984 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, and DESTINY-Lung02.
Contacts
Media Inquiries
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+1 302 885 2677
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US Media Mailbox: usmediateam@astrazeneca.com