9MO - Amivantamab, lazertinib and bevacizumab in EGFR-mutant advanced NSCLC with acquired resistance to 3rd generation EGFR-TKI: Final results from the phase II ETOP AMAZE-lung trial

Background

MET and angiogenic pathways are activated in EGFR-mutant NSCLC upon TKI resistance. Amivantamab (ami), an EGFR-MET bispecific antibody, is approved in combination with chemotherapy for EGFR-mutant NSCLC patients (pts) after progression on osimertinib (osi) based on the MARIPOSA-2 trial. We examined a chemo-sparing strategy for pts experiencing osi resistance.

Methods

AMAZE-lung (NCT05601973) is a prospective, international, single-arm, phase II trial, evaluating ami (

Results

Sixty-one pts were recruited (3/2023–5/2024) from 17 sites in Europe, with 9 months(m) median follow-up: median age 65 years, 70% female, 61% never-smokers, 82% white; 59% EGFR ex 19 del, 30% brain metastases.

Among the first 60 pts, response by 12w was confirmed for 20 pts (ORR 33%; 95.6% CI: 21%–47%), meeting the study prespecified criteria for success. Over the study duration, 24 of the 61 (39%) pts achieved PR (22 confirmed). The median DoR was 13.9 m (CI: 8.3-NE). The DCR was 79%, median PFS and OS were 10.9 m (CI: 5.3-NE) and 15.5 m (CI: 12.3-NE), respectively.

Common treatment-related (TR) AEs were infusion related reaction (58%), acneiform rash (50%), paronychia (42%) and fatigue (40%). TR venous thromboembolism of 3–4 and any grade were experienced by3% and 17% of pts, respectively. No fatal TRAEs were reported.

Conclusions

Ami-laz-bev combination demonstrated durable antitumour activity and represents a promising chemo-sparing alternative after progression on osi. Safety was consistent with known toxicity profiles.

Clinical trial identification

NCT05601973.

Legal entity responsible for the study

ETOP IBCSG Partners Foundation.

Funding

Janssen Pharmaceutica NV.

Disclosure

R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan, Janssen, Merck Serono, Puma Biotech, Thermo Fisher; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Pfizer. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Guardant Health, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx, AnHeart, Arcus Biosciences, Ellipses, Gilead, IO Biotech, Mirati; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Novocure, PharmaMar; Financial Interests, Institutional, Other, Subinvestigator: Amgen; Financial Interests, Institutional, Invited Speaker: Ariad, AstraZeneca, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, GSK, Takeda, Trizel, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Personal, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Personal, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role, Mesothelioma Committee, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Personal, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Personal, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Personal, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. A.J. De Langen: Financial Interests, Institutional, Advisory Board: AztraZeneca, MSD, BMS, Seagen; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, MSD, Merus. E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre, Genmab, Apollomics; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi, Illumina; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Transgene; Other, Personal, Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). P. Iranzo Gomez: Financial Interests, Personal, Invited Speaker: Takeda, Johnson&Johnson, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Pfizer, MSD; Financial Interests, Personal, Other, sponsored travel: Roche. M. Frueh: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Boehringer Ingelheim, Roche, Takeda, Pfizer, Janssen, Daiichi Sankyo, PharmaMar. M. Pérol: Financial Interests, Personal, Advisory Board, Advisory board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Esai, Ipsen, Novocure, AbbVie, Anheart Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Symposium: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Personal, Expert Testimony, Expert Testimony: AstraZeneca; Financial Interests, Personal, Invited Speaker, Steering Committee member: Lilly; Financial Interests, Institutional, Invited Speaker, Local PI: AbbVie, Amgen, Anheart Therapeutics, Apollomics, Arrivent Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Innate Pharma, Roche; Financial Interests, Institutional, Research Grant, Resarch grant: AstraZeneca, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Personal, Invited Speaker, Trial Chair: Anheart Therapeutics; Financial Interests, Personal, Invited Speaker, IDMC Chair: PharmaMar, Sophiagenetics; Financial Interests, Personal, Invited Speaker, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. G. Metro: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen. M.A. Sala Gonzalez: Financial Interests, Personal, Advisory Board: Roche Farma SA; Financial Interests, Personal, Invited Speaker, educational event: Pzifer SA, Deciphera. M. Cucurull Salamero: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Regeneron, Takeda. F.W.F. Cerciello: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, PharmaMar; Non-Financial Interests, Personal, Principal Investigator, Co-PI on a project of the Basic and Translational Science Committee of the IASLC: IASLC. A. Addeo: Financial Interests, Institutional, Advisory Board: BMS, AZD, Roche, Eli Lilly, Merck, J&J; Financial Interests, Personal, Advisory Board: Pfizer, Takaeda, MSD; Financial Interests, Institutional, Invited Speaker: Novartis. B. Ruepp: Financial Interests, Institutional, Full or part-time Employment: ETOP IBCSG Partners. U. Dafni: Financial Interests, Personal, Other, Member of the Tumor Agnostic Evidence Generation working Group: Roche; Financial Interests, Personal, Expert Testimony, Statistical review and assessment of a Clinical Trial: AstraZeneca; Non-Financial Interests, Personal, Leadership Role, Member of the BoD & Manager of this not for profit organization providing statistical expertise and support in Clinical trials, primarily in cancer: Frontier Science Foundation - HELLAS. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGBA317-A1217-301/AdvanTIG-301: Beigene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020–2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. R.A. Stahel: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Novocure, PharmaMar; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other, Co-Editor in Chief: Lung Cancer; Financial Interests, Personal, Other, Editor: CTR; Financial Interests, Institutional, Research Grant, ETOP study: Roche, AstraZeneca, BMS, MSD, Pfizer, Mirati, Janssen, Amgen, GSK; Financial Interests, Institutional, Research Grant, IBCSG study: Novartis, Ipsen, Pierre Fabre, MSD, Pfizer, Roche, AstraZeneca, Celgene; Non-Financial Interests, Personal, Member of Board of Directors, President Foundation Council: ETOP IBCSG Partners Foundation. All other authors have declared no conflicts of interest.