Abstract 59P
Background
Cohort C arm of the CHRYSALIS-2 study is evaluating amivantamab plus lazertinib (ami+laz) in participants (pts) with atypical EGFR-mutant (EGFRm; eg, G179X, S7681, L861Q) NSCLC. Pts with atypical EGFRm NSCLC have worse outcomes on EGFR tyrosine kinase inhibitors (TKIs) vs pts with common EGFRm NSCLC (Patil et al. 2020). We compared outcomes for 1L ami+laz (FDA and EMA approved for common EGFRm advanced NSCLC) vs 1L physician-selected EGFR TKI monotherapy from a matched real-world cohort of pts with atypical EGFRm advanced NSCLC.
Methods
CHRYSALIS-2 Cohort C (NCT04077463) enrolled pts with atypical EGFRm advanced NSCLC and an ECOG performance status score of 0–1. Pts with solitary or co-existing exon 20 insertions or common EGFR mutations were excluded. In this prespecified analysis, a trialmatched cohort of pts who received physician-selected 1L EGFR TKIs were identified from the NSCLC Flatiron Health/Foundation Medicine Clinico-Genomic Database (FH/FMI CGDB) between 01-Jan-2014 and 31-Mar-2024. Baseline patient characteristics were balanced between Cohort C and the real-world cohort using propensity score (PS) weighting. Overall survival (OS) and time to treatment discontinuation (TTD) were evaluated.
Results
From Cohort C, 49 pts who received 1L ami+laz were included. In the FH/FMI CGDB, 69 pts had received 1L EGFR TKIs; osimertinib (osi; 49%) and afatinib (afa; 41%) were most common. After PS weighting, effective real-world cohort sample size was 46 pts. OS was significantly longer in pts receiving ami+laz vs EGFR TKIs (HR, 0.29; 95% CI, 0.12–0.71; P=0.015); median OS was not estimable (NE; 95% CI, 26.3–NE) vs 19.6 mo (95% CI, 5.6–52.7), respectively. 24-mo OS rates were 77% for ami+laz vs 47% for EGFR TKIs (osi: 41%; afa: 55%). TTD was significantly longer in pts receiving ami+laz vs EGFR TKIs (HR, 0.44; 95% CI, 0.26–0.75; P=0.008), with a median TTD of 14.0 mo (95% CI, 8.2–27.6) vs 3.7 mo (95% CI, 1.6–17.1), respectively. 24-mo TTD rates were 41% for ami+laz vs 10% for EGFR TKIs.
Conclusions
Pts with atypical EGFRm advanced NSCLC who received 1L ami+laz had significantly improved survival outcomes compared to EGFR TKI monotherapy in the real-world setting.
Clinical trial identification
NCT04077463.
Editorial acknowledgement
Medical writing assistance was provided by Nick Harbin, PhD of Lumanity Communications Inc, and was funded by Johnson & Johnson.
Legal entity responsible for the study
Janssen Research & Development, LLC, a Johnson & Johnson Company.
Funding
Janssen Research & Development, LLC, a Johnson & Johnson Company.
Disclosure
P. Tomasini: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, BMS, Roche, Janssen, Amgen; Financial Interests, Personal, Other, Travel: Takeda, AstraZeneca, BMS. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Pfizer, Eli Lilly, BMS/Ono, Takeda, Janssen, IMBdx, Merck (German), Novartis, Abion, Beigene, ImmuneOncia, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Eli Lilly, Amgen, Yuhan; Financial Interests, Personal, Expert Testimony: Abion; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZeneca, Lunit. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Sharp & Dohme, Novartis, Regeneron, Turning Point, Pfizer, Genmab, Daiichi Sankyo, Johnson & Johnson, ITeos Therapeutics, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme, Gilead, Novartis, Regeneron, Johnson & Johnson, Pierre Fabre; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Financial Interests, Institutional, Invited Speaker: Nuvalent; Non-Financial Interests, Personal, Leadership Role, President (2021–2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulı.? A. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines, Regeneron, Lilly, Black Diamond Therapeutics, Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role/Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med, Regeneron, Loxo, Alkermes, Medikine, Black Diamond Therapeutics, Nalo Therapeutics, Scorpion Therapeutics, Arrivent Biopharma, GV20 Therapeutics. S. Michels: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Novartis; Pfizer; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Janssen; Novartis; Pfizer. E. Ichihara: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Takeda, Pfizer, Novartis, Chugai Pharma, MSD, Ono Pharmaceutical, Bristol Myers Squibb Japan; Financial Interests, Personal, Research Grant: Janssen. J. Neal: Financial Interests, Personal, Other, Honoraria: Biomedical Learning Institute; Clinical Care Options; CME Matters; HMP Education; Medical Educator Consortium; Medscape; MJH Life Sciences; Peerview; Prime Oncology; Projects in Knowledge; Research to Practice; Rockpointe CME; Financial Interests, Personal, Advisory Board: AbbVie; Amgen; AstraZeneca; Blueprint Medicines; Calithera Biosciences; D2G Oncology; Exelixis; Genentech/Roche; Gilead Sciences; Iovance Biotherapeutics; Jounce Therapeutics; Lilly; Mirati Therapeutics; Natera; Novartis; Novocure; Regeneron; Sanofi/Regen; Financial Interests, Personal, Research Grant: AbbVie (Inst); Adaptimmune (Inst); Boehringer Ingelheim (Inst); Exelixis (Inst); Genentech/Roche (Inst); GSK (Inst); Janssen (Inst); Merck (Inst); Nektar (Inst); Novartis (Inst); Takeda (Inst). L. Demirdjian: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. C.S. Meyer: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. H. Kanakamedala: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. A. Louder: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. L. Trani: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. I. LECONTE: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Baig: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. 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, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen; Financial Interests, Personal, Member of Board of Directors: J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; 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, PDX, PDO, PDC Licensing Contract – not patent: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, 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, JINTSbio, Hanmi, Vertical Bio AG, National Research Foundation of Korea, KHIDI, Therapex; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. All other authors have declared no conflicts of interest.