LBA5 - Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study

Background

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell–directing activity. Ami combined with carboplatin/pemetrexed (ami-chemo) demonstrated safety and antitumor activity in the phase 1 CHRYSALIS study. PAPILLON (NCT04538664) evaluated ami-chemo vs chemo in first-line EGFR Ex20ins advanced NSCLC.

Methods

Treatment-naïve pts were randomized 1:1 to ami-chemo or chemo. The primary endpoint was progression-free survival (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 the chemo arm upon progression.

Results

Overall, 308 pts were randomized (ami-chemo, 153; chemo, 155); median age was 61/62 years, 56/60% female, 64/59% Asian, and 23/23% with history of brain metastases for ami-chemo/chemo, respectively. At median follow-up of 14.9 months, the median PFS was 11.4 months (95% CI, 9.8–13.7) for ami-chemo vs 6.7 months (95% CI, 5.6–7.3) for chemo (hazard ratio [HR], 0.40; 95% CI, 0.30–0.53; P<0.001). The 18-month PFS rate was 31% for ami-chemo vs 3% for chemo. PFS benefit of ami-chemo was consistent across subgroups. ORR was 73% (95% CI, 65–80) for ami-chemo vs 47% (95% CI, 39–56) for chemo (odds ratio, 2.97; 95% CI, 1.84–4.79; P<0.001). Median PFS2 was not estimable for ami-chemo vs 17.2 months for chemo (HR, 0.49; 95% CI, 0.32–0.76; P=0.001). Interim OS analysis (33% maturity) showed a favorable trend for ami-chemo vs chemo (HR, 0.67; 95% CI, 0.42–1.09; P=0.106), despite 66%, of chemo-randomized pts whose disease had progressed, receiving second-line ami. The most common TEAEs (≥40%) for ami-chemo were neutropenia, paronychia, rash, anemia, infusion-related reactions, and hypoalbuminemia; no new safety signals. Discontinuation of ami due to treatment-related AEs was 7%.

Conclusions

Among pts with EGFR Ex20ins advanced NSCLC, ami-chemo achieved superior PFS vs chemo. Safety profile was consistent with that of each individual agent. PAPILLON establishes ami-chemo as the new first-line standard of care in EGFR Ex20ins advanced NSCLC.

Clinical trial identification

NCT04538664.

Editorial acknowledgement

Medical writing assistance was provided by Katharine Fang, PhD (Janssen Global Services LLC), with support from Claire E. Brady, PharmD and Jessica Swanner, PhD (Lumanity Communications Inc) and funded by Janssen Global Services LLC.

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Family member is an employee: AstraZeneca. K. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, Loxo, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, Johnson & Johnson, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: AstraZeneca, MSD Oncology. 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, Founder: DAAN Biotherapeutics. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AstraZeneca, Lilly, PharmaMar, Beigene, Daiichi, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President.ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. S. Cheng: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca. M. Thiagarajan: Financial Interests, Personal, Writing Engagement: Janssen Global Services LLC; Financial Interests, Personal, Member of Board of Directors: Malaysian Oncological Society. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech, Eli Lilly, Janssen, AbbVie, Gritstone; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Eli Lilly; Financial Interests, Institutional, Local PI: Genentech, Janssen, BMS, AbbVie. J.K. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. 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; Financial Interests, Personal, Steering Committee Member: 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. A.S. Mansfield: Financial Interests, Institutional, Research Grant: Novartis, Verily; Financial Interests, Institutional, Speaker, Consultant, Advisor: Rising Tide – grant reviewer, TRIPTYCH Health Partners Expert Think Tank, Janssen - steering committee, BeiGene, Chugai Pharmaceutical Co Ltd (Roche), Ideology Health LLC (formerly Nexus Health Media) - moderator, AXIS Medical Education, Inc. – CME presentation, Johnson & Johnson Global Services – steering committee, Intellisphere LLC (OncLive Summit Series) – CME presentation, Answers in CME – CME presentation, Immunocore - presentation; Financial Interests, Personal, Speaker, Consultant, Advisor: Antoni van Leeuwenhoek Kanker Instituut – CME presentation, University of Miami Int’l Mesothelioma Symposium – speaker; Financial Interests, Personal, Other, Travel: Shanghai Roche; Financial Interests, Institutional, Advisory Board: AbbVie Advisory Board, AstraZeneca Advisory Board, Bristol Myers Squibb Advisory Board, Genentech/Roche Advisory Board, Takeda Oncology; Non-Financial Interests, Personal, Member of Board of Directors: Mesothelioma Applied Research Foundation, Friends of Patan Hospital; Financial Interests, Personal, Research Funding, Study funding, article processing charges: Bristol Myers Squibb. J. Hung: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Roche, OnO Pharma, Eli Lilly and Company, Takeda, Boehringer Ingelheim, Pfizer, Chugai, Novartis, Janssen Pharma. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, Beigene, Takeda, Lilly, Roche, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Coordinating PI: Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, GSK, Trizel; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. J. Dias: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Janssen, Roche, Sanofi, Takeda; Financial Interests, Institutional, Other, Local subinvestigator: AbbVie, AstraZeneca, Beigene, Daiichi Sankyo, GSK, Lilly, Novartis, Regeneron, Sanofi, Takeda, Xcovery; Financial Interests, Institutional, Local PI: Amgen, Bristol-Myers Squibb, Debiopharm, Incyte Corporation, Ipsen, Janssen, Merck, Merck Sharp and Dohme, Roche; Other, Financial support for participation in scientific events: Amgen, Janssen. A. Bhattacharya: Financial Interests, Personal, Full or part-time Employment: Janssen. T. Agrawal: Financial Interests, Personal, Full or part-time Employment: Janssen. M. Shreeve: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson and Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson and Johnson. 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. All other authors have declared no conflicts of interest.