LBA14 - Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial

Background

Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, plus lazertinib (laz), a CNS-penetrant, 3^rd-generation EGFR TKI, have demonstrated antitumor activity in phase 1 studies. MARIPOSA (NCT04487080) evaluated ami+laz vs osimertinib (osi) in the first-line setting.

Methods

Patients (pts) with treatment-naïve, EGFR-mutated (Ex19del or L858R) locally advanced or metastatic NSCLC were randomized 2:2:1 to ami+laz, osi, or laz. Primary endpoint was progression-free survival (PFS) of ami+laz vs osi by blinded independent central review. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), PFS after first subsequent therapy (PFS2), and safety. CNS monitoring was required.

Results

1074 pts were randomized (ami+laz, 429; osi, 429; laz, 216). Baseline characteristics were balanced; median age was 63 years, 62% were female, 59% Asian, and 41% had a history of brain metastases. At a median follow-up of 22.0 months (mo), ami+laz showed a 30% reduction in the risk for disease progression or death vs osi (HR, 0.70; 95% CI, 0.58–0.85; P<0.001), with median PFS of 23.7 mo (95% CI, 19.1–27.7) vs 16.6 mo (95% CI, 14.8–18.5), respectively. ORR was 86% (95% CI, 83–89) for ami+laz vs 85% (95% CI, 81–88) for osi, with median DoR among confirmed responders of 25.8 mo (95% CI, 20.1–NE) vs 16.8 mo (95% CI, 14.8–18.5), respectively. Early PFS2 data favored ami+laz vs osi (HR, 0.75; 95% CI, 0.58–0.98). At interim OS, there was a favorable trend for ami+laz over osi (HR, 0.80; 95% CI, 0.61 to 1.05; P=0.1). EGFR- and MET-related AEs were higher for ami+laz except diarrhea, which was higher for osi. VTEs were increased for ami+laz, mostly grade 1-2, occurred early, and effectively managed with anticoagulants. ILD rates were low and similar across arms.

Conclusions

Ami+laz was statistically superior to osi, providing clinically meaningful improvement in PFS, with higher DoR and a favorable OS trend. The safety profile of ami+laz was consistent with prior reports. MARIPOSA establishes ami+laz as a new first-line, standard of care for EGFR-mutated advanced NSCLC.

Clinical trial identification

NCT04487080.

Editorial acknowledgement

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

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

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. 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. A.I. 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, Local PI: 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. 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. J. Lee: Financial Interests, Personal, Advisory Board: 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. Y.V. Ostapenko: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics. P. Danchaivijitr: Financial Interests, Personal, Financially compensated role, Honoraria: Roche, MSD, BMS, Janssen, Astellas; Financial Interests, Personal, Advisory Board: Roche, MSD, Janssen Astellas, Risai; Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, Janssen, BMS, Astellas, Risai; Financial Interests, Institutional, Advisory Board: MSD, Roche, Janssen. A. Alip: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim,CIPLA Malaysia, Eisai Msia, Ipsen, MSD; Financial Interests, Personal, Speaker’s Bureau: BMS, Ipsen, AstraZeneca, MCIgets India,MMI Malaysia; Financial Interests, Personal, Research Funding: jansen&Jansen, MSD, Novartis, Nova Satra Health, AstraZeneca. J. Dias: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Janssen, Roche, Sanofi, Takeda; Financial Interests, Institutional, Other, Local subinvestigator: AbbVie, AstraZeneca, Beigene, Daiichi Sankyo, GSK, Lilly, Novartis, Regeneron, Sanofi, Takeda, Xcovery; Financial Interests, Institutional, Local PI: Amgen, Bristol-Myers Squibb, Debiopharm, Incyte Corporation, Ipsen, Janssen, Merck, Merck Sharp and Dohme, Roche; Other, Financial support for participation in scientific events: Amgen, Janssen. T. Sun: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Martinez: Financial Interests, Full or part-time Employment: Johnson and Johnson; Financial Interests, Stocks/Shares: Johnson & Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. M. Shreeve: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Stocks/Shares: Johnson and Johnson. S. Sethi: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Stocks/Shares: Johnson & Johnson. R.E. Knoblauch: Financial Interests, Personal, Stocks/Shares: Johnson and Johnson; Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson. H. Hayashi: Financial Interests, Personal, Research Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co. Ltd., Nippon Boehringer lngelheim Co. Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sanko; Financial Interests, Personal, Speaker’s Bureau: Amgen K.K., AstraZeneca K.K., Boehringer lngelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., MSD K.K., Novartis Pharmaceuticals K.K., Ono Pharmace; Financial Interests, Personal, Advisory Board: AstraZeneca K.K., Boehringer lngelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Guardant Health (Manuscript fee), Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Merck Biopharma Co. Ltd.. All other authors have declared no conflicts of interest.