4O - Amivantamab plus lazertinib vs osimertinib in first-line (1L) EGFR-mutant (EGFRm) advanced NSCLC: Final overall survival (OS) from the phase III MARIPOSA study

Background

1L treatment of EGFRm advanced NSCLC with 3^rd-gen EGFR TKIs provides a median OS (mOS) of ~3 yrs, with ~25%–40% of pts not receiving second-line therapy. In MARIPOSA (NCT04487080; median follow-up: 22.0 mo), 1L amivantamab plus lazertinib (ami+laz) significantly improved progression-free survival vs osimertinib (osi) in pts with EGFRm advanced NSCLC (HR, 0.70; P < 0.001), with consistent benefit across risk groups. Favorable OS trends were seen for ami+laz vs osi at interim OS analysis and after 31.1 mo follow-up. Ami+laz is FDAand EMA-approved for 1L EGFRm advanced NSCLC. In FLAURA, which established osi as standard of care (SoC) for 1L EGFRm pts, osi extended median OS by ~7movs1^st-gen TKIs (mOS, 38.6 movs 31.8 mo). Here, we report the final analysis of OS for ami+laz vs osi from MARIPOSA.

Methods

Pts with previously untreated, EGFRm (Ex19del/L858R) advanced NSCLC were randomized 2:2:1 to receive ami+laz (n=429), osi (n=429), or laz (n=216; to assess contribution of components). Pts received IV ami (1050 mg; 1400 mg if ≥80 kg; weekly for 4weeks, every 2 weeks thereafter) plus 240 mg oral laz daily or 80 mg oral osi daily. OS for ami+laz vs osi was a key secondary endpoint with overall type I error rate controlled at 2-sided 5% across interim and final analyses. Protocol-prespecified final OS analysis was conducted when ~390 deaths occurred across both arms.

Results

At a median follow up of 37.8 mo, ami+laz demonstrated a statistically significant and clinically meaningful improvement in OS vs osi (HR for death, 0.75; 95% CI, 0.61–0.92; P < 0.005). Median OS was not estimable (NE; 95% CI, 42.9–NE) in the ami+laz arm vs 36.7 mo (95% CI, 33.4–41.0) in the osi arm. Assuming an exponential distribution of OS in both arms, ami+laz is anticipated to prolong median OS by at least 12mo vs osi. At 36 mo, 60% of pts were alive in the ami+laz arm vs 51% of pts in the osi arm. Additional endpoints will be presented.

Conclusions

Ami+laz is the first and only treatment to significantly reduce the risk of death vs osi in pts with 1L EGFRm advanced NSCLC. While the median has not yet been reached for ami+laz, it is expected to provide an OS benefit of at least 12 mo. These results further establish ami+laz as a new SoC in this population.

Clinical trial identification

NCT04487080.

Editorial acknowledgement

Medical writing assistance was provided by Suparna Abraham, PharmD of Lumanity Communications Inc, and was funded by Johnson & Johnson.

Legal entity responsible for the study

Janssen Research & Development, LLC, a Johnson & Johnson Company.

Funding

Janssen Research & Development, LLC, a Johnson & Johnson Company.

Disclosure

J.C. Yang: Financial Interests, Institutional, Advisory Board: AbbVie, Amgen, AnHeart Therpeutics, ArriVent, AstraZeneca, Bayer, Black Diamond Therapeutics Inc., Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GSK, Gilead, Janssen, MSD, Merck KGaA, Novartis, Ono Pharmaceuticals, Pfizer, Regeneron, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis; Financial Interests, Personal and Institutional, Invited Speaker, Travel to major meeting to present the trial results: AstraZeneca, Dizal Pharmaceutical; Financial Interests, Personal and Institutional, Invited Speaker, Travel to major meeting to present the trial result: Merck Sharp & Dohme Corporation; Financial Interests, Personal, Invited Speaker: Numab Therapeutics AG, Merck KGaA, Ipsen, Takeda Oncology, Daiichi Sankyo, Eli Lilly, Janssen Pharmaceuticals, ArriVent, Amgen, Bayer, Yuhan Pharmaceuticals, Black Diamond Therapeutics Inc.; Non-Financial Interests, Personal, Member: IASLC, ASCO. 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, Beigene, ImmuneOncia, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Eli Lilly, Amgen, Yuhan; Financial Interests, Personal, Expert Testimony: Abion; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZeneca, Lunit. S. Lu: Financial Interests, Personal, Other, Consulting Fees: AstraZeneca, Pfizer, Boehringer Ingelheim, HUTCHMED, Simcere Pharmaceutical, Zai Lab, GenomiCare, Yuhan Corporation, Roche, Menarini, InventisBio Co. Ltd.; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Hansoh Pharma, Jiangsu Hengrui, HUTCHMED, Bristol Myers Squibb, BeiGene, Eli Lilly. A. Alip: Non-Financial Interests, Personal, Advisory Role, Advisory for neoadjuvant therapy for lung cancer: AstraZeneca; Non-Financial Interests, Personal, Advisory Role, Ad board meeting for neoadjuvant treatment for NSCLC: BMS; Non-Financial Interests, Personal, Principal Investigator, Mariposa trial: Janssen. J. Dias: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Amgen, Janssen, Roche, Sanofi; Financial Interests, Personal, Other, Travel: Amgen, Janssen; Financial Interests, Personal, Research Grant: BMS Brazil, Merck, Ipsen, Novartis, Roche, Janssen, MSD, Amgen, Beigene, Debiopharm Group. P. Danchaivijitr: Financial Interests, Institutional, Research Grant: MSD, AstraZeneca, Roche; Financial Interests, Personal, Speaker’s Bureau: MSD, AstraZeneca, Roche, BMS; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, BMS. N. Girard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Regeneron, AbbVie, Amgen, Lilly, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen, Pierre Fabre, Beigene; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Pfizer, Amgen, MSD, Sanofi, Gilead, Janssen; Financial Interests, Personal, Officer: edimark; 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. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Sharp & Dohme, Novartis, Regeneron, Turning Point, Pfizer, Genmab, Daiichi Sankyo, Johnson & Johnson, ITeos Therapeutics, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme, Gilead, Novartis, Regeneron, Johnson & Johnson, Pierre Fabre; 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; Financial Interests, Institutional, Invited Speaker: Nuvalent; 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. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd, Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co.Ltd; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Institutional, Invited Speaker: IQVIA Services Japan K.K, Syneos Health Clinical K.K., EPS Corporation., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K. K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co., Ltd,., Covance Japan Inc., EP-CRSU CO., LTD., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Caner Research Organization, Ono Pharmaceutical Co., Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co., Ltd.; Financial Interests, Institutional, Funding: SRL Medisearch Inc., Eisai Inc., Thoracic Oncology Research Group(TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Personal, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. 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, Regeneron, Lilly, Black Diamond Therapeutics, Sanofi; 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, Regeneron, Loxo, Alkermes, Medikine, Black Diamond Therapeutics, Nalo Therapeutics, Scorpion Therapeutics, Arrivent Biopharma, GV20 Therapeutics. B. Besse: Financial Interests, Institutional, Advisory Board: AbbVie, Biontech SE, Beijing Aviston Biotechnology, BristolMyerSqibb, CureVac AG, PharmaMar, Sanofi aventis, Regeneron; Financial Interests, Institutional, Expert Testimony: AbbVie, BristolMyerSqibb, Eli Lilly, Ellipse pharma Ltd, CureVac AG, F. Hoffmann-La Roche Ltd, Foghorn Therapeutics Inc., Genmab, Immunocore, Owkin, Sanofi; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, BristolMyerSqibb, MSD, Daiichi Sankyo, Eli Lilly, Ose Immunotherapeutics, Sanofi, Servier, OSE immunotherapeutics, Sanofi, Takeda, Genmab, Taiho, AstraZeneca, Amgen, Beigene, CureVac, Janssen, MSD, PharmaMar, Eli Lilly, Daiichi Sankyo, Enliven, Nuvalent, Ellipsis, Prelude Therapeutics; Non-Financial Interests, Personal, Leadership Role, Chair of the Scientific Chairs Council: EORTC; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Board: IFCT. T. Sun: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Ennis: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. S. Sethi: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; 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; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen; Financial Interests, Personal, Member of Board of Directors: 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, PDX, PDO, PDC Licensing Contract – not patent: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, 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, Vertical Bio AG, National Research Foundation of Korea, KHIDI, Therapex; 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. All other authors have declared no conflicts of interest.