Abstract 1109P
Background
E20i, the 3rd most common EGFR mutation, is largely resistant to EGFR tyrosine kinase inhibitors (TKIs). In the single-arm CHRYSALIS study, aNSCLC E20i patients showed durable responses to amivantamab, an EGFR-MET bispecific antibody targeting tumors with activating and resistant EGFR mutations. This study compares the effectiveness of amivantamab to current systemic anti-cancer therapies in RW practice in Japan.
Methods
External control (EC) patients were selected by applying CHRYSALIS eligibility to data from LC-SCRUM-Asia. EC patients were included for every qualifying Line of Therapy (LOT) after platinum-based (plt) chemotherapy. Average treatment effect on the treated was used to weight EC patients to adjust for differences in characteristics from CHRYSALIS. Outcomes were compared between EC patients, and all and Asian-only CHRYSALIS patients using weighted Cox proportional hazards regression models for progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS), and generalized estimating equations with repeated measurements for overall response rate (ORR).
Results
115 CHRYSALIS and 94 EC patients were identified. Among 309 LOTs, post-plt EC patients received docetaxel (22.0%), immuno-oncology (21.7%), and EGFR TKIs (19.1%). Compared to EC patients, amivantamab-treated patients had significant risk reduction in PFS (HR [95% CI]: 0.59 [0.45-0.78]; median PFS: 6.7 vs 4.7 months), TTNT (HR: 0.39 [0.29-0.53]; median TTNT: 12.2 vs 5.1 months), and death (HR: 0.59 [0.40-0.88]; median OS: 19.9 vs 14.1 months), and significantly higher ORR (41.7% vs 14.1%, p<0.001). Analyses of amivantamab-treated Asian patients (n=61) showed similar clinical benefit compared to EC patients.
Conclusions
Amivantamab-treated patients had significantly longer PFS, TTNT and OS, and significantly higher ORR than patients treated with RW therapies in the post-plt chemotherapy setting in Japan. This reflects the benefit of amivantamab after plt chemotherapy for aNSCLC E20i patients, compared to current therapies. While effects of E20i variants were not explored, first use of specific therapies were examined in a post-hoc analysis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Janssen Asia Pacific.
Funding
Janssen.
Disclosure
.M. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Janssen, Novartis, Takeda; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Non-Financial Interests, Principal Investigator: AstraZeneca/MedImmune, Boryung, Hanmi, Janssen, Boehringer Ingelheim, Novartis, Takeda, Sanofi, Roche/Genentech, Merck Sharp & Dohme Corp, Merck Serono, Regeneron, Genmab, Bayer. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Officer, International Thymic malignancy interest group, President: ITMIG; Other, Family member is an employee: AstraZeneca. G. Low Massin: Financial Interests, Institutional, Full or part-time Employment: Janssen; Financial Interests, Institutional, Stocks/Shares: Janssen. J. Zhou, D.Y. Yu, Y. Yang, M. Murota: Financial Interests, Institutional, Full or part-time Employment: Janssen. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint Medicines; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Brigebio Therapeutics, Cyrus Therapeutics, Guardant Health, Joseah Bio; Financial Interests, Personal, Invited Speaker: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, Kanaph Therapeutic Inc, Cyrus Therapeutics, Interpark Bio Convergence Corp; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Other, Founder: Daan Biotherapeutics. All other authors have declared no conflicts of interest.