790MO - Phase I study of fianlimab, a human lymphocyte activation gene-3 (LAG-3) monoclonal antibody, in combination with cemiplimab in advanced melanoma (mel)

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-(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 additional 12 months if clinically indicated). Tumour measurements were performed 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 (AI) 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 patients 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 was provided by Jenna Lee, MSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc.

Funding

Regeneron Pharmaceuticals, Inc.

Disclosure

O. Hamid: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Novartis, Pfizer, Sanofi, 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. 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; Non-Financial Interests, Personal, Advisory Role, Uncompensated relationships: Bayer, Boryung, Novartis, Regeneron Pharmaceuticals, Inc., Roche/Genentech, Sanofi. M.A. 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, GlaxoSmithKline, IDEAYA Biosciences, Ikena Oncology, ImmVira Pharma, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, MedImmune, Mereo BioPharma, Metabomed, Moderna, NBE Therapeutics, Nektar, Novartis, Oncorus, PACT Pharma, Pfizer, Plexxikon, Prelude Therapeutics, Pyramid Biosciences, Regeneron Pharmaceuticals, Inc., Sapience Therapeutics, Scholar Rock, Seattle Genetics, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics; Financial Interests, Institutional, Advisory Role: Astellas Pharma, AstraZeneca, BicycleTX Limited, Castle Biosciences, Eisai, Ideaya Biosciences, iTeos, Moderna, Pfizer, Regeneron Pharmaceuticals, Inc; Financial Interests, Invited Speaker: Tizona Therapeutics, TMUNITY Therapeutics, TopAlliance Biosciences, and Xilio. N.J. Lakhani: Financial Interests, Personal, Advisory Role: Innovent Biologics, Ikena, S.K. Life Sciences; Financial Interests, Personal, Research Grant: Innovent Biologics, Alexo Therapeutics, Ascentage Pharma, Asana Biosciences, BeiGene, Constellation Pharmaceuticals, Alexion Pharmaceuticals, Cerulean Pharma, Forty Seven, Loxo, Macrogenics, Merck, Pfizer, Regeneron Pharmaceuticals, Inc., Formation Biologics, Coordination Therapeutics, Symphogen, CytomX Therapeutics, InhibRx, Incyte, Jounce Therapeutics, Livzon, Northern Biologics, Tesaro, Innovent Biologics, LAM Therapeutics, Ikena, Celgene, Shattuck Labs, Alpine Immune Sciences, Genmab, Odonate, Mersana, Seagen, Alpine Biosciences, Astellas Pharma, Celgene, Helsinn Therapeutics, Ikena Oncology, Lilly, Sapience Therapeutics, Epizyme, Gilead, GlaxoSmithKline, Tizona, and Servier. J. Kaczmar: Financial Interests, Personal, Advisory Role: Bicara Therapeutics, Rakuten Medical, Regeneron Pharmaceuticals, Inc. K.P. Papadopoulos: Financial Interests, Personal, Advisory Role: Basilea, 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 Therapeutics, Peloton Therapeutics, Pfizer, Regeneron Pharmaceuticals, Inc., Syros Pharmaceuticals, Tempest Therapeutics, and Treadwell Therapeutics. S. Chen: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: 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. G. Kroog: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. T. Sims: 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. 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.