513MO - Amivantamab plus chemotherapy vs chemotherapy as a first-line treatment among Asian patients with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): PAPILLON subgroup analysis

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell–directing activity. In the global, phase 3 PAPILLON study (NCT04538664), ami and carboplatin-pemetrexed (ami-chemo) significantly improved progression-free survival (PFS) vs chemo (data submitted to ESMO 2023) in treatment naïve patients (pts) with Ex20ins advanced NSCLC. The incidence of EGFR mutations is higher among Asian pts than other races. Thus, we evaluated ami-chemo vs chemo in Asian pts by race from PAPILLON.

Methods

Pts were randomized 1:1 to ami-chemo or chemo. The primary endpoint was PFS by blinded independent central review. Secondary endpoints included objective response rate (ORR), PFS after first subsequent therapy (PFS2), overall survival (OS), and safety. Crossover to ami monotherapy was allowed for pts in the chemo arm who progressed.

Results

186/308 randomized pts were Asian (ami-chemo, 97; chemo, 89); median age was 57/62 years, 56%/58% female, and 21%/25% had a history of brain metastases for ami-chemo/chemo, respectively. At a median follow up of 16.6 months, the median PFS for Asian pts was 11.5 months (95% CI, 9.8–13.7) for ami-chemo vs 5.6 months (95% CI, 4.9–7.0) for chemo (HR, 0.34; 95% CI, 0.23–0.49; P<0.001); this was comparable to the overall population. The 18-month PFS rate was 31% for ami-chemo vs 3% for chemo. ORR was 70% (95% CI, 60–79) for ami-chemo vs 51% (95% CI, 40–62) for chemo (odds ratio, 2.16; 95% CI, 1.19–3.93; P=0.012). Median PFS2 was not estimable for ami-chemo vs 18.8 months for chemo (HR, 0.46; 95% CI, 0.26–0.83; P=0.008). Median interim OS was not estimable vs 24.4 months for ami-chemo vs chemo (HR, 0.65; 95% CI, 0.34–1.24; P=0.189) despite crossover among chemo-randomized pts who had progressed. AE rates in Asian pts were similar to the overall PAPILLON population. Most common ami-chemo TEAEs (>50%) were paronychia, neutropenia, rash, anemia, and leukopenia; no new safey signals. Discontinuation of ami due to treatment-related AEs was 8%.

Conclusions

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

Clinical trial identification

NCT04538664.

Editorial acknowledgement

Claire E. Brady of Lumanity Communications Inc.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

C. Zhou: Financial Interests, Personal, Invited Speaker, Honoraria: Eli Lily, Roche, Sanofi, Qilu Pharma, Hengrui, Innovent Biologics, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc; Financial Interests, Personal, Invited Speaker, BI: BI; Financial Interests, Personal, Invited Speaker, MSD: MSD; Financial Interests, Personal, Advisory Board, Advisor: Amoy Diagnositics. S. Kitazono: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Ono Pharmaceutical Co, Chugai Pharmaceutical Co., Ltd. A. Ono: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Local PI: Janssen Research&Development. M. Thiagarajan: Non-Financial Interests, Personal, Leadership Role, President: Malaysian Oncological Society. J. Hung: Financial Interests, Personal, Financially compensated role: AstraZeneca, Roche, Ono Pharma, Eli Lilly, Takeda, BI, Pfizer, Chugai, Novartis, Janssen. M. Boyer: Financial Interests, Personal, Research Funding: Janssen, Amgen, AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Eli Lilly, Imugene, Daiichi Sankyo, Dizal. J. Xie, A. Bhattacharya, M. Baig, T. Agrawal, R.E. Knoblauch: 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, 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. All other authors have declared no conflicts of interest.