LBA11 - Amivantamab plus chemotherapy vs chemotherapy among Asian patients with <italic>EGFR</italic>-mutant advanced NSCLC after progression on osimertinib: A MARIPOSA-2 subgroup analysis

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant, 3^rd-generation EGFR tyrosine kinase inhibitor. In the global, phase 3 MARIPOSA-2 study (NCT04988295), ami plus carboplatin-pemetrexed (chemo) significantly improved progression-free survival (PFS) vs chemo (hazard ratio [HR], 0.48 [95% confidence interval [CI], 0.36–0.64]; P<0.001). The highest prevalence of EGFR-mutated NSCLC is seen in Asian populations. We evaluated ami-chemo vs chemo in Asian patients (pts) by race from MARIPOSA-2.

Methods

Pts were randomized 2:2:1 to ami-laz-chemo, chemo, or ami-chemo. Because the ami-laz-chemo arm was modified during the study, data on this arm will be reported after longer follow-up. Here, we report the primary endpoint of PFS for ami-chemo vs chemo by blinded independent central review per RECIST v1.1. Secondary endpoints include objective response rate (ORR), intracranial PFS, and safety.

Results

Of 657 total pts randomized, 63/131 and 127/263 Asian pts were randomized to the ami-chemo and chemo arms, respectively. At a median follow up of 9.5 mo, ami-chemo showed a 46% reduction in the risk for disease progression or death vs chemo (HR, 0.54; 95% CI, 0.37–0.81; P=0.002), with a median PFS of 6.8 vs 4.2 mo, which was comparable to the overall population. ORR was 66% (95% CI, 53–78) for ami-chemo vs 32% (95% CI, 24–41) for chemo (odds ratio, 4.04 [95% CI, 2.13–7.67]; P<0.001). Median intracranial PFS was 12.45 mo for ami-chemo vs 8.5 mo for chemo (HR, 0.58; 95% CI, 0.34–1.00; P=0.049). AE rates in Asian pts were similar to the overall MARIPOSA-2 population. The most common TEAEs in the ami-chemo arm were neutropenia and thrombocytopenia, which were transient, nonserious, occurred largely during Cycle 1, and were associated with low rates of febrile neutropenia and bleeding complications.

Conclusions

Ami-chemo demonstrated superior PFS vs chemo in Asian pts. Hematologic toxicities were more frequent in the ami-chemo arm, but were generally transient and of low clinical impact. These results were consistent with those of the overall population.

Clinical trial identification

NCT04988295.

Editorial acknowledgement

Claire E. Brady of Lumanity Communications Inc.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Global Services LLC.

Disclosure

J. Shih: Financial Interests, Personal, Research Grant: Roche, Genconn Biotech; Financial Interests, Personal, Invited Speaker: ACT Genomics, Amgen, Genconn Biotech, AstraZeneca, Roche, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharma, Takeda, CStone Pharmaceuticals, Janssen, TTY Biopharm, Orient EuroPharma, MundiPharma, GSK, Lotus Pharma; Financial Interests, Personal, Other: AstraZeneca, Roche, and Chugai Phar; Financial Interests, Personal, Advisory Board: Takeda. J. Wang: Financial Interests, Personal, Invited Speaker: AZ, Pfizer, BeiGene. 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. K. Azuma: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd. T. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., ONO Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co LTD., Bristol Myers Squibb, Amgen Inc., Eli Lilly Japan K.K.; Financial Interests, Institutional, Local PI: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., ONO Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Amgen inc., Merck Biopharma Co., Ltd., AnHeart Therapeutics; Financial Interests, Institutional, Coordinating PI: Eli Lilly Japan K.K. C.C. Lin: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Takeda, BMS, Roche, Merck. S. Ganguly: Financial Interests, Institutional, Other: Novartis, AstraZeneca and Janssen Global Services. P. Chu, S. Shah, B. Diorio, J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen. 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, GI Innovation, 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. All other authors have declared no conflicts of interest.