Abstract LBA54
Background
In the phase 3 MARIPOSA-2 study (NCT04988295), amivantamab (ami)-chemotherapy (chemo; carboplatin/pemetrexed) showed superior progression-free survival (PFS) vs chemo in patients (pts) with EGFR-mutant, advanced non-small cell lung cancer (NSCLC) after progression on osimertinib (osi; HR, 0.48; 95% CI, 0.36–0.64; P<0.001). At the first interim analysis (IA) of overall survival (OS; median follow-up: 8.7 mo), a favorable trend was seen for ami-chemo vs chemo (HR, 0.77; 95% CI, 0.49–1.21). Second IA (IA2) of OS and post-progression results are reported.
Methods
MARIPOSA-2 enrolled pts with EGFR-mutant (Ex19del/L858R) advanced NSCLC post-osi. The primary endpoint was PFS. IA2 of OS was prespecified to occur when ∼75% of total OS events were observed. OS was to be evaluated at a 2-sided alpha of 0.0142 (O’Brien-Fleming alpha spending approach as implemented by the Lan-DeMets method). Other endpoints were time to treatment discontinuation (TTD), time to subsequent therapy (TTST), and PFS after first subsequent therapy (PFS2).
Results
At IA2, 208 OS events were observed across both arms. After a median follow-up of 18.1 mo (clinical cutoff: 26-Apr-2024), OS was numerically improved for ami-chemo vs chemo (median, 17.7 vs 15.3 mo; HR, 0.73; 95% CI, 0.54–0.99; P=0.039), but did not reach the prespecified significance threshold. At 18 mo, 50% vs 40% of pts were alive with ami-chemo vs chemo. The OS benefit of ami-chemo vs chemo was generally consistent among pre-defined subgroups. PFS2 was significantly prolonged for ami-chemo vs chemo (median, 16.0 vs 11.6 mo; HR, 0.64; 95% CI, 0.48–0.85; P=0.002) and improved over time, supporting the OS findings. TTD and TTST were significantly prolonged in favor of ami-chemo. Table: LBA54
Efficacy outcomes
| Endpoint | Ami-chemo (n=131) | Chemo (n=263) |
| Median follow-up, mo | 18.6 | 17.8 |
| OS events, n (%) | 65 (50) | 143 (54) |
| Median OS, mo (95% CI) | 17.7 (16.0–22.4) | 15.3 (13.7–16.8) |
| HR for OS (95% CI) | 0.73 (0.54–0.99); P=0.039 | |
| 18-mo OS rate, % (95% CI) | 50 (40–59) | 40 (33–46) |
| Median TTD, mo (95% CI) | 10.4 (7.9–11.6) | 4.5 (4.2–5.0) |
| HR for TTD (95% CI) | 0.42 (0.33–0.53); PConclusionsAmi-chemo numerically improved OS and significantly prolonged post-progression outcomes vs chemo in EGFR-mutant, advanced NSCLC post-osi. Clinical trial identificationNCT04988295. Editorial acknowledgementMedical writing assistance was provided by Claire E. Brady, PharmD, of Lumanity Communications Inc and funded by Janssen Global Services LLC. Legal entity responsible for the studyJanssen Research & Development. FundingJanssen Global Services LLC. DisclosureS. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, Takeda, Lilly, Roche, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx, AnHeart, Arcus Biosciences, Ellipses, Gilead, IO Biotech, Mirati; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Novocure, PharmaMar; 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 Committee, 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 Advisory Board Member, Unpaid: Lung Cancer Europe. K.L. Reckamp: Financial Interests, Personal, Other, consultant: AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GSK, Janssen, Lilly, Mirati, Novartis; Financial Interests, Personal, Advisory Board: EMD Soreno; Financial Interests, Institutional, Local PI: Genentech, Blueprint, Calithera, Daiichi Sankyo, Elevation Oncology, Janssen. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Pfizer, Eli Lilly, BMS/Ono, Takeda, Janssen, IMBdx, Merck (German), Novartis, Abion, Abion, BeiGene, ImmuneOncia, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Eli Lilly, Amgen, Yuhan; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZeneca, Lunit. B. Melosky: Financial Interests, Personal, Speaker’s Bureau: Pfizer, BMS, Merck, Roche, Janssen, AstraZeneca, Takeda, Jazz, BI, EMD Serono, Novartis, Sanofi; Financial Interests, Personal, Other, Attending meetings and/or travel: Pfizer, Sanofi, Janssen. J. Wang: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, BeiGene. M.R. García Campelo: Financial Interests, Personal, Other, Honoraria: Pfizer, Novartis, Roche, Lilly, AstraZeneca, Takeda, MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Novartis, Roche, Lilly, AstraZeneca, Takeda, MSD; Financial Interests, Speaker’s Bureau: Pfizer, Novartis, Roche, Lilly, AstraZeneca, Takeda, MSD. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer, Genmab; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, 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., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Financial Interests, Institutional, Local PI: Nuvalent; 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. 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; Other, Family member is an employee: AstraZeneca. R.D. Gentzler: Financial Interests, Institutional, Research Funding: Janssen, Pfizer, Amgen, Chugai, Merck, AstraZeneca, Janssen, Daiichi Sankyo, Alliance Foundation, Takeda, ECOG/ACRIN, Jounce Therapeutics, Bristol Myers Squibb, NCI, Big Ten Research Consortium, Hoosier Cancer Research Network, SWOG, Helsinn; Financial Interests, Personal, Other, Honoraria for lecture: 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, Member: ASCO Scientific Review Committee, NCI Investigational Drug Steering Committee; Financial Interests, Personal, Trial Chair: Hoosier Cancer Research Network, Thoracic Clinical Trial Working Group; Financial Interests, Personal, Other, Associate Editor: Journal of Clinical Oncology, ASCO Meeting Abstracts. W. Nassib William Junior: Financial Interests, Personal, Invited Speaker: Amgen, Genentceh / Roche, Eli Lilly, BMS, Pfizer, Janssen, United Medical; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Merck, Bayer, Sanofi, Takeda, Novartis. T. Takahashi: Financial Interests, Personal, Research Grant: AstraZeneca K.K., Pfizer Japan, Inc., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Boehringer Ingelheim Japan, Inc., and Pfizer Japan, Inc; Financial Interests, Personal, Other, Personal Fees: Roche Diagnostics (Pleasanton, CA, USA) K.K. M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Caris Life Sciences, Daiichi Sankyo, Novartis, EMD Serono, Janssen, Lilly, Pfizer, Genentech, Mirati, Regeneron, Silverback; Financial Interests, Personal, Invited Speaker: Takeda, Blueprint; Financial Interests, Personal, Other, Travel: AnHeart. J.M. Bauml, S. Shah, B. Diorio, P. Chu: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. 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, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; 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, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, 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, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Founder: Daan Biotherapeutics; Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd.. A. Passaro: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, eCancer; Financial Interests, Personal and Institutional, Steering Committee Member, Steering Committee Member PALOMA-3 trial: Janssen; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Janssen; Financial Interests, Personal and Institutional, Local PI: MSD; Financial Interests, Personal and Institutional, Steering Committee Member: Arrivent, Bayer; Financial Interests, Institutional, Coordinating PI: Cullinan Oncology; Non-Financial Interests, Other, Scientific Committee for Lung Cancer Guideline: AIOM; Non-Financial Interests, Officer, ESMO Council Member & Chair of Communication Committee: ESMO; Non-Financial Interests, Officer, Chair of Communication Committee: ESMO; Non-Financial Interests, Officer, Council Member: ESMO. All other authors have declared no conflicts of interest. 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