Abstract 150P
Background
Concurrent blockade of LAG-3 may enhance efficacy of anti-programmed cell death-1 (PD-1) therapies. We previously presented safety and efficacy data from the phase 1 study in patients (pts) with advanced mel treated with anti-LAG-3 (fianlimab) in combination with anti-PD-1 (cemiplimab). We demonstrated high clinical activity among pts with anti–PD-1/PD-ligand (L)1-naive (expansion cohort [EC] 6 and 15) advanced mel. Among pts in EC6+EC15 (N=80), the objective response rate (ORR) was 63.8%, the disease control rate (DCR) was 80.0%, and the median duration of response (mDOR) was not reached (NR). Factors associated with a poorer prognosis and reduced response to immunotherapy in pts with advanced mel include advanced stage of disease, elevated lactate dehydrogenase (LDH) levels, and metastasis sites, including liver or other visceral organs (M1c).
Methods
Pts with advanced mel were treated with fianlimab 1600 mg and cemiplimab 350 mg intravenously every 3 weeks for 12 months. In this subgroup analysis we evaluated fianlimab and cemiplimab in pts with advanced mel with poor prognostic features. ORR, DCR and mDOR are reported here for pts with liver mets at baseline (BL), LDH>upper limit of normal (ULN) at BL, and LDH>ULN at BL and M1c stage in pts in EC6+EC15.
Results
As of 1 July 2022, data cutoff date, 80 pts in EC6+EC15 (40 pts each) were treated with fianlimab and cemiplimab. For EC6+EC15 combined, at BL,19 pts (23.8%) had liver mets, 28 pts (35.0%) had LDH>ULN; and 13 pts (16.3%) had LDH>ULN at BL and any M1c. In pts with liver mets at BL, the ORR for EC6+15 combined was 47.4%, the DCR was 63.2%, and the mDOR was 9.0 months (95% confidence interval [CI], 2.8–not evaluable [NE]). In pts with LDH>ULN at BL, the ORR for EC6+15 was 57.1%, the DCR was 71.4, and the mDOR was NR (95% CI, 7.3–NE). In pts with LDH>ULN at BL and any M1c, the ORR for EC6+15 was 53.8%, the DCR was 69.2%, and the mDOR was NR (95% CI, 5.7–NE).
Conclusions
Despite small numbers in subgroups, the efficacy analysis from EC6 and EC15 combined demonstrates high activity of fianlimab in combination with cemiplimab in pts with advanced mel and poor prognosis features at BL.
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
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. K. Lewis: Financial Interests, Personal, Other, Honoraria: Array BioPharma, Iovance Biotherapeutics; Financial Interests, Personal, Advisory Role: Array BioPharma, Iovance Biotherapeutics, Merck, Roche, Regeneron Pharmaceuticals, Inc., Sanofi; Financial Interests, Personal, Research Grant: Alkermes, Amgen, Array BioPharma, Bristol Myers Squibb, Incyte, Iovance Biotherapeutics, Kartos Therapeutics, Merck, Nektar, Neon Therapeutics, OncoSec, Regeneron Pharmaceuticals, Inc., Replimune, Roche/Genentech, Senhwa Biosciences, Ultimovacs; Financial Interests, Personal, Other, Travel, accommodation, or expenses: Alkermes, Merck, Neon Therapeutics, Regeneron Pharmaceuticals, Inc., Roche/Genentech; Financial Interests, Personal, Other, Uncompensated relationships: Roche/Genentech, Regeneron Pharmaceuticals, Inc. 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: Astellas Pharma, AstraZeneca, BicycleTX Limited, Castle Biosciences, Eisai, Ideaya Biosciences, iTeos, Moderna, Pfizer, 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. Thomas: Financial Interests, Personal, Speaker’s Bureau: Amgen, BMS, Genentech, Ipsen, Merck, Novartis, Pfizer. J. Kaczmar: Financial Interests, Personal, Advisory Role: Bicara Therapeutics, Rakuten Medical, and 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, Cerulean Pharma, Forty Seven, Loxo, Macrogenics, Merck, Pfizer, Regeneron Pharmaceuticals, Inc., Apexian Pharmace. 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. K. Kim: Financial Interests, Personal, Advisory Board: Bristol-Myers Squib, Genentech Inc., Novartis, Regeneron and Sanofi; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Novartis, Merck, Regeneron and Sanofi. G. Rabinowits: Financial Interests, Personal, Advisory Role: Castle, EMD Serono, Pfizer, Merck, Regeneron Pharmaceuticals, Inc., Sanofi; Financial Interests, Personal, Stocks/Shares: Syros Pharmaceuticals and Regeneron Pharmaceuticals, Inc. A.S. Spira: Financial Interests, Personal, Stocks/Shares: Lilly; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, Bayer; Financial Interests, Personal, Advisory Role: Array BioPharma, Incyte, Amgen, Novartis, AstraZeneca/MedImmune, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Merck, Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, LAM Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb,. J. Mani: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. S. Chen: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: 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.