5MO - Effect of amivantamab dose interruptions on efficacy and safety of first-line amivantamab plus lazertinib in EGFR-mutant advanced NSCLC: Exploratory analyses from the MARIPOSA study

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant 3rd-generation EGFR TKI. As first-line treatment, ami+laz demonstrated superior progression-free survival (PFS) vs osimertinib in patients (pts) with EGFR-mutant advanced non-small cell lung cancer (NSCLC; Cho Ann Oncol 2023). Protocol guidance in the MARIPOSA study (NCT04487080) recommended an ami dose interruption in the case of related grade ≥2 toxicity. For pts treated with first-line ami+laz, the majority of key adverse events occurred in the first 4 months (mo; Spira JTO 2023). We studied the efficacy and safety in ami+laz pts that had ami dose interruptions in the first 4 months.

Methods

This analysis included all pts who were randomized to the ami+laz arm in MARIPOSA (efficacy set: n=429, safety set: n=421). Study protocol dictated ami to be dose modified before laz. Dose interruptions were defined as any interruptions of ami due to any cause.

Results

Among the 429 pts who were randomized to the ami+laz arm, 421 received at least one dose. At a median follow-up of 22.0 months, 49% (206/421) had ami dose interruptions in the first 4 months of treatment. Among pts who required ami dose interruptions in the first 4 months, the median PFS was 23.9 mo (95% CI, 18.5–NE). Median PFS, objective response rate (ORR), and median duration of response (DoR) for pts with and without dose interruptions of ami in the first 4 months were similar to all pts randomized to the ami+laz arm, as shown in the table. Updated analyses, including the impact of dose interruptions on treatment tolerability, will be presented at the time of the meeting. Table: 5MO

Efficacy endpoints among patients with and without ami dose interruptions within the first 4 months of receiving Ami+Laz

CI, confidence interval; NE, not estimable *Event-free rate shown as percentage (95%CI)

Conclusions

Among pts receiving ami+laz, early dose modifications of ami per protocol guidance did not adversely impact the efficacy of the combination. Ami+laz is a new first-line standard of care for pts with EGFR-mutant advanced NSCLC.

Clinical trial identification

NCT04487080.

Editorial acknowledgement

Katharine Fang, PhD (Janssen Global Services), with support from Lumanity Communications Inc.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

M.R. García Campelo: Financial Interests, Personal, Other, Consulting Fees: AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Janssen Oncology; MSD Oncology; Novartis; Pfizer; Roche/Genentech; Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Janssen Oncology; Lilly; MSD Oncology; Novartis; Pfizer; Roche; Sanofi/Aventis; Takeda; Financial Interests, Personal, Other, Travel: MSD Oncology; Pfizer; Roche/Genentech. 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 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, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, 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. 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, Personal, Other, Family member is an employee: AstraZeneca. H. Yoshioka: Financial Interests, Personal, Invited Speaker, Lecture fee: Eli Lilly Japan K.K., Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisor: Delta-Fly Pharma; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Janssen Pharmaceutical, MSD, Novartis Pharma, Delta-Fly Pharma, Boehringer Ingelheim. J. Lee: Financial Interests, Personal, Other, Consulting Fees: Yuhan Corporation. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck, Pfizer, Lilly, BMS/Ono, Takeda, Janssen, IMBdx; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck, Lilly, Amgen; Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Lunit. M.A.N. Sendur: Financial Interests, Personal, Advisory Board: BMS, Pfizer, Takeda, Roche, Astellas; Financial Interests, Personal, Invited Speaker: Astellas, Pfizer, BMS, MSD, Roche. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Beigene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd, 4D Pharma; Financial Interests, Institutional, Expert Testimony: AbbVie, Da voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD, AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi Sankyo, GSK, Janssen, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Turning Point Therapeutics, Genmab, Taiho, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Funding: Cristal Therapeutics. A. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med. 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; 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, Invited Speaker, 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; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Guardant Health, BeiGene, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche; 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, 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 Task-force Member, 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 Advisory Board Member, Unpaid: Lung Cancer Europe. P. Mahadevia, S. Sethi, J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. All other authors have declared no conflicts of interest.