2MO - Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR exon 20 insertion-mutated advanced NSCLC: Analysis of post-progression endpoints from PAPILLON

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. In PAPILLON (NCT04538664), ami plus carboplatin-pemetrexed (ami-chemo) significantly prolonged progression-free survival (PFS) vs chemo in patients (pts) with EGFR Ex20ins advanced NSCLC (Zhou NEJM 2023). We evaluated post-progression secondary endpoints of time to treatment discontinuation (TTD) and time to subsequent (systemic anticancer) therapy (TTST).

Methods

308 pts were randomized (ami-chemo: 153; chemo: 155). Chemo-randomized pts were allowed crossover upon blinded independent central review (BICR)-confirmed progression. TTD and TTST were evaluated based upon site reporting of participant treatment changes.

Results

At a median follow-up of 14.9 months (mo), 54% (83/153) and 85% (131/155) of pts discontinued treatment in the ami-chemo and chemo arms, respectively. Median TTD was 13.2 mo for ami-chemo vs 7.5 mo for chemo (HR, 0.38 [95% CI, 0.28–0.51]; P<0.0001). Median TTST was 17.7 mo for ami-chemo vs 9.9 mo for chemo (HR, 0.35 [95% CI, 0.25–0.49]; P<0.0001). These findings are consistent with PFS after first subsequent therapy (PFS2; HR, 0.49 [95% CI, 0.32–0.76]; P=0.001) and interim overall survival (HR, 0.67 [95% CI, 0.42–1.09]; P=0.11) favoring ami-chemo vs chemo (Girard Ann Oncol 2023). Among pts who discontinued, 52% (43/83) and 72% (94/131) in the ami-chemo and chemo arms started a subsequent therapy, most common being chemotherapy (ami-chemo; 30% [13/43]) and ami monotherapy (chemo; 76% [71/94]). 17% (11/63 with disease progression) of pts continued treatment beyond progression in the ami-chemo arm, median duration after progression of 40.4 weeks (95% CI, 8.7–NE). Among 71 chemo-randomized pts who received second-line ami monotherapy, 65 pts were part of the study crossover arm, with 6 receiving ami off protocol. Among the 65 pts in the crossover arm, 46% (30/65) discontinued ami monotherapy. Median treatment duration was 4.9 mo (range, 0–18.2), with a median TTD of 9.7 mo (95% CI, 6.7–11.0).

Conclusions

Ami-chemo significantly prolonged TTD and TTST vs chemo. Ami-chemo is the new first-line standard of care for EGFR Ex20ins-mutant advanced NSCLC.

Clinical trial identification

NCT04538664.

Editorial acknowledgement

Medical writing assistance was provided by Lumanity Communications Inc and funded by Janssen Global Services LLC.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

E. Felip: Financial Interests, Personal, Funding: Grant For Oncology Innovation (Merck Healthcare KGAa). Fundación Merck Salud; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Sanofi, Takeda, Bergenbio. C.A. Shu: Financial Interests, Personal, Advisory Board: Janssen, AstraZeneca, Genentech, Gilead, Arcus Biosciences, Takeda, Mirati. M.R. García Campelo: Financial Interests, Personal, Advisory Board: AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Janssen Oncology; MSD Oncology; Novartis; Pfizer; Roche/Genentech; Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Janssen Oncology; Lilly; MSD Oncology; Novartis; Pfizer; Roche; Sanofi/Aventis; Takeda; Financial Interests, Personal, Other, Travel: MSD Oncology; Pfizer; Roche/Genentech. A. Delmonte: Financial Interests, Personal, Research Grant: Roche, MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel: Roche, MSD; Financial Interests, Personal, Advisory Board: Novartis. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. N. Girard: Financial Interests, Personal, Other, Consulting Fees: AbbVie, Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Hoffmann-La Roche, Janssen, LeoPharma, Lilly, Merck Sharp & Dohme, Novartis, Sivan, Mirati, Pfizer, Sanofi, Takeda; Financial Interests, Personal, Speaker’s Bureau: AbbVie, Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Hoffmann-La Roche, Janssen, LeoPharma, Lilly, Merck Sharp & Dohme, Novartis, Sivan, Mirati, Pfizer, Sanofi, Takeda; Financial Interests, Personal, Other, Travel: Janssen, Amgen, BMS; Financial Interests, Personal, Advisory Board: Hoffman-La Roche. A.S. Mansfield: Financial Interests, Institutional, Research Grant: Novartis, Verily; Financial Interests, Institutional, Other, Consulting Fees: Rising Tide, TRIPTYCH Health Partners; Financial Interests, Institutional, Speaker’s Bureau: Janssen, BeiGene, Chugai Pharmaceutical Co Ltd (Roche), Ideology Health LLC, AXIS Medical Education, Inc., Johnson & Johnson Global Services, Intellisphere LLC, Immunocore; Financial Interests, Personal, Invited Speaker: Antoni van Leeuwenhoek Kanker Instituut, University of Miami Int’l Mesothelioma Symposium; Financial Interests, Personal, Other, Travel: Shanghai Roche; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Takeda Oncology; Financial Interests, Personal, Member of Board of Directors: Mesothelioma Applied Research Foundation, Friends of Patan Hospital; Financial Interests, Personal, Funding: Bristol Myers Squibb. K. Park: Financial Interests, Personal, Advisory Board: JNJ, AstraZeneca, Daiichi Sankyo, Eli Lilly, Samsung Medical Center; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Other, DMC member: BeiGene, Incyte; Financial Interests, Personal, Other, Advisor/Consultant: Genius, IMBdx; Financial Interests, Personal, Other, Advisor: ABION; Financial Interests, Personal, Stocks/Shares, Stock option: IMBDx, GENIUS. C. Zhou: Financial Interests, Personal, Other, Consulting Fees: Innovent Biologics Qilu, Hengrui, TopAlliance Biosciences Inc; Financial Interests, Personal, Speaker’s Bureau: Eli Lily China, Sanofi, BI, Roche, MSD Qilu, Hengrui, Innovent Biologics, Alice C-Stone, LUYE Pharma, TopAlliance Biosciences Inc，Amoy Diagnositics, AnHeart . K. Xia, A. Bhattacharya, M. Wade, M. Baig,T. Agrawal, P. Mahadevia, R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.E. Sanborn: Financial Interests, Personal, Advisory Board: AstraZeneca, EMD Serono, Daiichi Sankyo, Lilly Oncology, Janssen Oncology, Macrogenics, Sanofi Aventis, Regeneron, Mirati Therapeutics, GSK, G1 Therapeutics; Financial Interests, Personal, Invited Speaker: Illumina, GSK, Janssen Oncology; Financial Interests, Institutional, Funding, Funding for investigator-sponsored trial: Merck, AstraZeneca; Financial Interests, Institutional, Other, Institutional research support: BMS; Financial Interests, Institutional, Funding, Clinical trial funding: Jounce. All other authors have declared no conflicts of interest.