LBA15 - Amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib: MARIPOSA-2, a phase III, global, randomized, controlled trial

Background

Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, plus carboplatin-pemetrexed (chemo) with and without lazertinib (laz), a CNS-penetrant, 3^rd-gen EGFR TKI, have demonstrated antitumor activity in phase 1 studies. MARIPOSA-2 (NCT04988295) evaluated these combinations in EGFR-mutated (Ex19del or L858R) advanced NSCLC after disease progression on osimertinib (osi).

Methods

Patients (pts) were randomized 2:2:1 to ami-laz-chemo, chemo, or ami-chemo. Dual primary endpoints were progression-free survival (PFS) of ami-chemo vs chemo and ami-laz-chemo vs chemo by blinded independent central review. Secondary endpoints included objective response rate (ORR), overall survival (OS), intracranial PFS, and safety. During the study, hematologic toxicities in the ami-laz-chemo arm necessitated a regimen change to start laz after carboplatin completion.

Results

In total, 657 pts were randomized (ami-chemo, 131; ami-laz-chemo, 263; chemo, 263). Baseline characteristics were balanced between arms, including the number of pts with a history of CNS metastases (44%–46%). At a median follow-up of 8.7 mo, PFS was significantly improved with ami-chemo (HR, 0.48; 95% CI, 0.36–0.64) and ami-laz-chemo (HR, 0.44; 95% CI, 0.35–0.56) vs chemo (median PFS, 6.3 and 8.3 vs 4.2 mo, respectively; P<0.001 for both). ORR was 64% for ami-chemo and 63% for ami-laz-chemo vs 36% for chemo (P<0.001 for both). Interim OS was immature; HR of 0.77 (95% CI, 0.49–1.21) for ami-chemo vs chemo and HR of 0.96 (95% CI, 0.67–1.35) for ami-laz-chemo vs chemo. Median intracranial PFS was 12.5 mo for ami-chemo and 12.8 mo for ami-laz-chemo vs 8.3 mo for chemo (HR, 0.55 and 0.58; P=0.001 and P<0.001, respectively). Predominant AEs in the ami-containing arms were hematologic, EGFR, and MET-related. Ami-chemo had lower rates of hematologic AEs than ami-laz-chemo. The impact of modifying the ami-laz-chemo regimen on safety and efficacy requires longer follow-up.

Conclusions

Ami-chemo and ami-laz-chemo improved PFS, ORR, and intracranial PFS vs chemo in EGFR-mutated advanced NSCLC after progression on osi and may represent a new standard of care.

Clinical trial identification

NCT04988295.

Editorial acknowledgement

Medical writing assistance was provided by Katharine Fang, PhD (Janssen Global Services LLC), with support from Jessica Swanner, PhD and Jill Kolesar, PhD (Lumanity Communications Inc) and funded by Janssen Global Services LLC.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

A. Passaro: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Jansenn, Pfizer, Roche, Bayer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Jansenn, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, eCancer; Financial Interests, Institutional, Steering Committee Member, Steering Committee Member PALOMA-3 trial: Jansenn; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Jansenn; Non-Financial Interests, Other, Scientific Commitee for Lung Cancer Guideline: AIOM; Non-Financial Interests, Officer, ESMO Council Member & Chair of Communication Committee: ESMO. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Founder: DAAN Biotherapeutics. Y. Wang: Non-Financial Interests, Principal Investigator: Shanghai Pharmaceuticals Holding Co., Hengrui Pharmaceuticals Holding Co., Janssen Pharmaceutical Ltd., AstraZeneca. B. Melosky: Financial Interests, Personal, Invited Speaker: Pfizer, BMS, Merck, Roche, Janssen, AstraZeneca, Takeda, Jazz, BI, EMD Serono, Novartis, Sanofi; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pfizer, Sanofi, Janssen. R. Califano: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Lilly Oncology, Roche, Pfizer, MSD, Takeda, Amgen, Bayer, Janssen and Novartis, Sanofi, GSK and PharmaMar; Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly Oncology, Roche, Pfizer, MSD, Takeda, Amgen, GSK and Janssen; Financial Interests, Personal, Other, speaker in educational activities: Medscape, TOUCHIME and PEERVOICE; Financial Interests, Personal, Ownership Interest, partnership: The Christie Private Care - LOC; Financial Interests, Personal, Stocks/Shares: Supportive care UK; Financial Interests, Institutional, Local PI, principal investigator for clinical trial: Roche, AstraZeneca, Pfizer, Clovis, Lilly Oncology, MSD, BMS, AbbVie, Takeda, Janssen, and Novartis; Financial Interests, Institutional, Local PI: PharmaMar and GSK; Non-Financial Interests, Member, member of Lung Cancer Group: EORTC. S. Lee: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca/MedImmune, Lilly, Merck, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, BMS/Ono, IMBdx, Janssen, Lilly, Merck, Pfizer, Roche, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca, Lunit, Merck. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Family member is an employee: AstraZeneca. K.L. Reckamp: Financial Interests, Personal, Other, consultant: Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GSK, Janssen, Lilly, Mirati, Takeda; Financial Interests, Personal, Advisory Board: EMD Soreno, Merck KGA; Financial Interests, Personal, Writing Engagement: Seattle Genetics,; Financial Interests, Institutional, Local PI: Genentech, Blueprint, Calithera, Daiichi Sankyo, Elevation Oncology, Janssen. T. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co Ltd., Bristol-Myers Squibb, Amgen Inc., Eli Lilly Japan K.K.; Financial Interests, Institutional, Local PI: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Amgen inc., Merck Biopharma CO., LTD, AnHeart Therapeutics; Financial Interests, Institutional, Coordinating PI: Eli Lilly Japan K.K.,. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, Glaxo Smith Kline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol-Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., Glaxo Smith Kline Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. R.D. Gentzler: Financial Interests, Institutional, Research Funding: Janssen, Pfizer, Amgen, Chugai, Merck, AstraZeneca, Janssen, Daiichi Sankyo, Alliance Foundation, Takedo, ECOG/ACRIN, Jounce Therapeutics, Bristol Myers Squibb, NCI, Big Ten Research Consortium, Hoosier Cancer Research Network, SWOG, Helsinn; Financial Interests, Personal, Invited Speaker: Clinical Care Options, OncLive, Targeted Oncology, Society for Immotherapy of Cancer (SITC); Financial Interests, Personal, Other, Travel support for attending meetings: International Association for the Study of Lung Cancer (IASLC); Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Gilead, Janssen, Mirati, Daiichi Sankyo, Sanofi, Oncocyte, Jazz Pharmaceuticals, BluePrint Medicines; Financial Interests, Personal, Other, Co-chair: Hoosier Cancer Research Network, Thoracic Clinical Trial Working Group; Financial Interests, Personal, Member: ASCO Scientific Review Committee, NCI Investigational Drug Steering Committee; Financial Interests, Personal, Other, Associate Editor: Journal of Clinical Oncology, ASCO Meeting Abstracts. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, Beigene, Takeda, Lilly, Roche, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Coordinating PI: Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, GSK, Trizel; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. W. Nassib William Junior: Financial Interests, Personal, Invited Speaker: Amgen, BMS, Eli Lilly, Genentech / Roche, Janssen, Pfizer, United Medical; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Merck, Novartis, Sanofi, Takeda; Financial Interests, Personal, Expert Testimony: Boeringher Ingelheim. T. Sun: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. S. Shah: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. B. Diorio: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. M.R. García-Campelo: Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria and Speakers' Bureau: Pfizer, Novartis, Roche, Lilly, AstraZeneca, Takeda, MSD. J. Wang: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Pfizer, BeiGene.