Abstract 127P
Background
Concurrent blockade of LAG-3 may enhance efficacy of anti–programmed cell death-1 (anti–PD-1) therapies. We present safety and clinical activity data from a phase 1 study in patients (pts) with NSCLC treated with anti–LAG-3 (fianlimab) + anti–PD-1 (cemiplimab).
Methods
Pts with unresectable stage IIIB–C or IV NSCLC who were anti–PD-1/PD-L1-naive (expansion cohort [EC] 1) or anti–PD-1/L1-experienced within 3 months (mo) of screening (EC2) were eligible. Pts received fianlimab 1600 mg + cemi 350 mg intravenously every 3 weeks (wks) for 12 mo.
Results
As of the 1 July 2022 data cutoff, 15 EC1 and 15 EC2 pts were treated. For EC1 and EC2 respectively, median age was 70.0 and 67.0 years, 73.3% and 73.3% were male, and 33.3% and 73.3% were White. 40.0% of pts in EC1 were systemic treatment-naive. In EC2, 53.3% of pts had at least two lines of therapy including anti–PD1/L1 therapy. Median treatment duration was 12.1 wks and median follow-up was 8.5 mo and 5.4 mo for EC1 and EC2 respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) and serious TEAEs occurred in 33.3% & 20.0% and 40.0% & 13.3% of EC1 and EC2 pts, respectively. One pt in EC1 and no pts in EC2 discontinued due to a TEAE. No treatment-related deaths were reported. RECIST 1.1-based investigator-assessed objective response rate (ORR) was 26.7% (four partial responses [PRs]) in EC1 and 6.7% (one PR) in EC2. In EC1, the ORR for treatment-naive pts (n=6) was 50%; the ORR for pts with PD-L1 expression ≥50% (n=3) was 100%. Kaplan–Meier estimation of median progression-free survival was 2.6 mo (95% confidence interval [CI], 1.2–8.3) in EC1 and 4.1 mo (95% CI, 1.3–6.2) in EC2 pts. Median duration of response was not reached in EC1 and was 4.8 mo (95% CI, not evaluable [NE]–NE) in EC2. Fianlimab concentrations in serum in pts were similar in both EC1 and EC2 cohorts. LAG-3 and PD-L1 correlative biomarker analysis will be included in the presentation.
Conclusions
Fianlimab + cemiplimab demonstrated promising signs of clinical activity with durable responses among pts with anti–PD-1/L1-naive NSCLC and in pts with PD-L1 expression ≥50%, with a similar safety profile and with no new safety signals compared to cemiplimab monotherapy.
Clinical trial identification
NCT03005782.
Editorial acknowledgement
Medical writing and editorial support provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc.
Funding
Regeneron Pharmaceuticals, Inc.
Disclosure
B.C. Cho: Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan Corporation, Ono Pharmaceutical, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Ono Pharmaceutical, Yuhan Corporation, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Medpacto, and Blueprint Medicines; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics, BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, and Joseah Biopharma; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corporation and Gencurix Inc.; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics, Cyrus Therapeutics, and Interpark Bio Convergence Corporation; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. T.M. Kim: Financial Interests, Personal, Advisory Role: AstraZeneca/MedImmune, BeiGene, Boryung, F. Hoffmann-La Roche Ltd/Genentech, Inc, Janssen, Novartis, Sanofi, Takeda, Yuhan; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Uncompensated relationship: Bayer, Boryung, Novartis, Regeneron Pharmaceuticals, Inc., Roche/Genentech, and Sanofi. D. Sarker: Financial Interests, Personal, Other, Nonfinancial support: Medivir and MiNA Therapeutics; Financial Interests, Personal, Other, Personal fees and nonfinancial support: Eisai and Ipsen; Financial Interests, Personal, Other, Personal fees: AAA, AstraZeneca, Bayer, MSD, Sirtex, and Surface Oncology; Financial Interests, Personal, Research Grant: UCB. O. Hamid: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Novartis, Pfizer, Sanofi and Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Advisory Role: Aduro Biotech, Akeso Biopharma, Amgen, Arcus Biosciences, Bioatla, Bristol Myers Squibb, CytomX Therapeutics, Exelixis, Genentech, GlaxoSmithKline, Idera, Immunocore, Incyte, Iovance Biotherapeutics, Merck, Merck Serono, Moderna Therapeutics, NextCure, No. S. Williamson: Financial Interests, Personal, Research Grant: Novartis. H. Hatim: Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Eli Lilly, Pfizer, and Roche Sequencing Solutions; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Blueprint Medicine, and Janssen; Financial Interests, Personal, Advisory Role: AstraZeneca, Blueprint Medicine, Foundation Medicine, Merck, Mirati Therapeutics, Neogenomics, Takeda and Turning Point Therapeutics. S. Chen: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. J. Mani: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. V. Jankovic: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. A.J. Paccaly: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. S. Masinde: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. L. Brennan: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.