LBA10 - Amivantamab plus lazertinib vs osimertinib as first-line treatment among Asian patients with <italic>EGFR</italic>-mutated, advanced non-small cell lung cancer (NSCLC): MARIPOSA subgroup analysis

Background

Amivantamab (ami) is a bispecific antibody targeting EGFR and MET with immune-directing activity. Lazertinib (laz) is an oral, central nervous system (CNS)-penetrant, 3^rd-generation EGFR tyrosine kinase inhibitor. In the global, phase 3, randomized, controlled MARIPOSA study (NCT04487080) ami-laz significantly improved progression-free survival (PFS) vs osimertinib (osi) in patients (pts) with previously untreated, EGFR-mutated, advanced NSCLC. The incidence of EGFR mutations is higher among Asian pts than other races. Thus, we evaluated the efficacy and safety of ami-laz vs osi in Asian pts based on the MARIPOSA trial.

Methods

Pts were randomized 2:2:1 to receive ami-laz, osi, or laz. The primary endpoint was PFS based on blinded independent central review per RECIST v1.1. Secondary endpoints included objective response rate (ORR), duration of response (DoR), and safety.

Results

Of 1074 total randomized pts, 629 were Asian, with 250/429 and 251/429 randomized to the ami-laz and osi arms, respectively. Among Asian pts, median age was 63 years, 61%/57% female, and 44%/43% had a history of brain metastases for ami-laz/osi. At a median follow-up of 22.5 mo, ami-laz showed a 35% reduction in the risk of disease progression or death vs osi for Asian pts (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.50–0.83; P<0.001), with a median PFS of 27.5 vs 18.3 mo, which was comparable to the overall population. ORR was 88% (95% CI, 84–92) for ami-laz vs 85% (95% CI, 80–90) for osi (odds ratio, 1.29; 95% CI, 0.76–2.17). Median DoR among confirmed responders was 26.1 mo for ami-laz vs 17.5 mo for osi. Adverse event (AE) rates in Asian pts were similar to the overall MARIPOSA population. EGFR- and MET-related AEs were higher for ami-laz except diarrhea, which was higher for osi. VTEs were increased for ami-laz, but events were mostly grade 1-2 (no grade 4-5 events), occurred in the first 4 months of treatment, and were effectively managed with anticoagulants. ILD rates were low and similar across arms.

Conclusions

Ami-laz demonstrated superior PFS vs osi in Asian pts with a tolerable safety profile. These results were consistent with those of the overall population.

Clinical trial identification

NCT04487080.

Editorial acknowledgement

Claire E. Brady of Lumanity Communications Inc.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co., Ltd., Roche, Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Roche, Hansoh, BeiGene, Lilly Suzhou Pharmaceutical Co. Ltd.; Financial Interests, Personal, Coordinating PI: FibroGen. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boheringer 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, Personal, Other, Founder: DAAN Biotherapeutics. J. Lee: Financial Interests, Personal, Speaker, Consultant, Advisor: 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. P. Danchaivijitr: Financial Interests, Personal, Research Funding: MSD, AstraZeneca, Roche (All through institution); Financial Interests, Personal, Speaker’s Bureau: MSD, AstraZeneca, Roche, BMS; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, BMS. S.H. How: Financial Interests, Personal, Research Funding: Pfizer, MSD, AZ, Janssen, Roche, Novartis, Amgen, Arcus, Gilead, Merck; Financial Interests, Personal, Speaker’s Bureau: MSD, AZ, Amgen; Financial Interests, Personal, Advisory Board: MSD, AZ, Janssen, Roche, Amgen. J.C. Yang: Financial Interests, Personal, Other, institutional fee for advisory or consultancy services: Amgen, Bayer, BI, BMS; Financial Interests, Personal, Other, grant, institutional fee for advisory or consultancy services: AstraZeneca; Financial Interests, Personal, Other, Institutional fee for advisory or consultancy services: Daiichi Sankyo, Eli Lilly, Merck KGaA, Darmstadt, Germany, Merck Sharp & Dohme, Novartis, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals, JNJ; Financial Interests, Personal, Other, advisory or consultancy service: Ono Pharma, Pfizer; Financial Interests, Personal, Other, institutional fee for advisory services: Puma Technology, Gilead, GSK. 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, Local PI: Daiichi Sankyo, AstraZeneca, Janssen Pharmaceutical, MSD, Novartis Pharma; Financial Interests, Institutional, Coordinating PI: Delta-Fly Pharma, Boehringer Ingelheim. K. Xia, M. Martinez, J.M. Bauml, S. Sethi: Financial Interests, Personal, Full or part-time Employment: Janssen. H. Hayashi: Financial Interests, Personal, Research Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol Myers Squibb Co. Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sank; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim 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: Advisory board AstraZeneca K.K., Boehringer Ingelheim 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., and Merck Biopharma. All other authors have declared no conflicts of interest.