400P Phase I study of fianlimab, a human lymphocyte activation gene-3 (LAG-3) monoclonal antibody, in combination with cemiplimab in advanced melanoma (mel)

Document Type

Conference Proceeding

Publication Date

9-1-2022

Abstract

Background: Concurrent blockade of LAG-3 may enhance efficacy of anti-programmed cell death-1 (PD-1) therapies. We present updated safety and clinical activity data from patients (pts) with advanced mel treated with concurrent anti-LAG-3 (fianlimab) and anti-PD-1 (cemiplimab). Methods: This Phase 1 study included pts with unresectable or metastatic mel (excluding uveal mel) who were anti–PD-ligand (L)1 treatment naïve (expansion cohort [EC] 6) or anti–PD-(L) 1 experienced within 3 months of screening (EC7). Pts received fianlimab 1600 mg + cemiplimab 350 mg intravenously every 3 weeks for 12 months (optional extra 12 months if clinically indicated). Tumour measurements were taken every 6 weeks for 24 weeks, then every 9 weeks. Results: As of the 9 Feb 2022 data cutoff date, 40 EC6 and 15 EC7 pts were enrolled and treated with fianlimab + cemiplimab. For EC6 and EC7 cohorts respectively, median age was 69.5 and 59.0 years, 62.5% and 46.7% were male, 90.0% and 60.0% were White. Median treatment duration was 37.1 weeks (EC6) and 9.0 weeks (EC7). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 37.5% (EC6) and 46.7% (EC7) of pts; serious TEAEs occurred in 32.5% (EC6) and 33.3% (EC7) of pts; 17.5% (EC6) and 13.3% (EC7) of pts discontinued treatment due to a TEAE. Rate of adrenal insufficiency was 12.5% (EC6) and 6.7% (EC7); none led to treatment discontinuation. Investigator-assessed objective response rate was 62.5% (6 complete responses; 19 partial responses [PRs]) in EC6 and 13.3% (2 PRs) in EC7 pts. Kaplan-Meier estimation of median progression-free survival was 14.2 (95% CI: 5.6–not estimated) months in EC6 and 1.4 (95% CI: 1.3–7.7) months in EC7 pts. Median duration of response had not been reached in both cohorts. LAG-3 and PD-L1 correlative biomarkers analysis will be included in the presentation. Conclusions: Fianlimab + cemiplimab in advanced mel pts had a similar safety profile to anti–PD-1 agents; clinical activity in anti-PD-(L)1-naïve pts appears higher than previously reported for anti-PD-1 monotherapy or anti–LAG-3 + anti–PD-1. A phase 3 trial (NCT05352672) investigating fianlimab + cemiplimab in advanced mel pts is ongoing. Clinical trial identification: NCT03005782. Editorial acknowledgement: Medical writing support and typesetting was provided by Jenna Lee of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc. Funding: Regeneron Pharmaceuticals, Inc. Disclosure: O. Hamid: 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. 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 relationships: Bayer, Boryung, Novartis, Regeneron Pharmaceuticals, Inc., Roche/Genentech, and Sanofi. M. Mckean: Financial Interests, Institutional, Research Grant: Alpine Immune Sciences, Arcus Biosciences, Arvinas, Ascentage Pharma Group, Bayer, Bicycle Therapeutics, BioMed Valley Discoveries, BioNTech, Dragonfly Therapeutics, EMD Serono, Epizyme, Erasca, Exelixis, Foghorn Therapeutics, Genentech, Gilead Sciences,; Financial Interests, Institutional, Advisory Role, payments to institution: Astellas Pharma, AstraZeneca, BicycleTX Limited, Castle Biosciences, Eisai, Ideaya Biosciences, iTeos, Moderna, Pfizer, Regeneron Pharmaceuticals, Inc. N. Lakhani: Financial Interests, Personal, Advisory Role: Innovent Biologics, Ikena, and S.K. Life Sciences; Financial Interests, Personal, Research Grant: Innovent Biologics, Alexo Therapeutics, Ascentage Pharma, Asana Biosciences, BeiGene, Constellation Pharmaceuticals, Alexion Pharmaceuticals, erulean Pharma, Forty Seven, Loxo, Macrogenics, Merck, Pfizer, Regeneron Pharmaceuticals, Inc., Apexian Pharmace. J. Kaczmar: Financial Interests, Personal, Advisory Role: Bicara Therapeutics, Rakuten Medical, and Regeneron Pharmaceuticals, Inc. K. Papadopoulos: Financial Interests, Personal, Advisory Role: Basilea and Turning Point Therapeutics; Financial Interests, Personal, Research Grant: 3D Medicines, AbbVie, ADC Therapeutics, Amgen, Anheart Therapeutics, Bayer, Calithera Biosciences, Daiichi Sankyo, EMD Serono, F-star, Incyte, Jounce Therapeutics, Lilly, Linnaeus Therapeutics, MabSpace Biosciences, MedImmune, Merck, Mersana, Mirati Thera. S. Chen, J. Mani, V. Jankovic, G. Kroog, G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. T. Sims: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment, current employee of AbbVie; was employed by Regeneron at the time the research was conducted: AbbVie. I. Lowy: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc., Sanofi, Genentech. All other authors have declared no conflicts of interest.

Issue

S7

First Page

S1598

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