Long-term follow-up of advanced melanoma (unresectable/metastatic

BackgroundTreatment (Tx) with FIAN (anti-lymphocyte activation gene-3 [LAG-3]) + CEMI (anti-programmed cell death protein 1 [PD-1]) had a 61% ORR in pts with aMel by investigator assessment with an acceptable risk–benefit profile. Here, we present an efficacy analysis by BICR with 12-months (mos) additional follow-up and safety data on pts with aMel.MethodsThis study (NCT03005782) enrolled 3 independent expansion cohorts of pts who were anti–PD-(L)1 Tx-naïve for aMel. Pts received FIAN 1600 mg + CEMI 350 mg IV every 3 weeks (wk) up to 24 mos.Results98 pts [median (med) age: 68 years (y)] were enrolled. As of data cutoff (31 October 2023), med follow-up was 23 mos, and med Tx duration was 36 wk. Grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and immune-mediated adverse event (imAEs) occurred in 47%, 39% and 39% of pts, respectively; 21% of pts discontinued Tx due to a TEAE. Rates of imAEs were similar to PD-1 monotherapy, except for adrenal insufficiency (12% [all grades] and 5% [grade ≥3]). BICR-assessed efficacy data for cohorts MM1, MM2, and MM3 are shown in the Table. Per BICR, overall (N=98) CR, ORR, and med PFS was 25%, 57% (95% CI: 47–67), and 24 mos (95% CI: 12–NE), respectively; med time to response and CR was 1.5 and 4.1 mos, respectively. Disease control rate was 78% (95% CI: 68–85), with med overall survival NR (95% CI: 42–NE). 31% and 4% of pts completed 1-y and 2-y Tx; med duration of response was NR (95% CI: 23–NE). ORR was 50% and 71% in pts with PD-L1 <1% and ≥1%; and 50% and 61% in pts with LAG-3 <1% and ≥1%, respectively. Circulating tumour DNA was cleared by Cycle 4 Day 1 in 15/31 pts. Table: 1097P Efficacy per BICR MM1 Initial cohort (n=40) MM2 Confirmatory cohort (n=40) MM3 neo/adjuvant experienced cohort (n=18) MM1+MM2+MM3 (N=98) Prior anti-PD-1 treatment in adjuvant/neoadjuvant setting (n=13) Liver metastasis (n=20) LDH > ULN (n=31) Objective Response Rate (ORR) (95% CI) 60% (43–75) 63% (46–77) 39% (17–64) 57% (47–67) 46% (19–75) 35% (15–59) 55% (36–73) Complete Response (CR) 23% 25% 28% 25% 31% 0 13% Progression-Free Survival (PFS), median (95% CI), months NR (8–NE) 19 (8–NE) 12 (1–NE) 24 (12–NE) NR (1–NE) 7 (1–NE) 14 (4–NE) CI, confidence interval; LDH, lactate dehydrogenase; NR: Not reached; NE: not estimated; MM: metastatic melanoma; ULN, upper limit of normal. ConclusionsWith longer follow up, FIAN + CEMI in aMel pts showed persistent high clinical activity by BICR regardless of PD-L1 or LAG-3 status and across high-risk subgroups with an acceptable safety profile. The prevalence of CRs increased over time.Clinical trial identificationNCT03005782.Editorial acknowledgementMedical writing support was provided by Dhara Patel, PhD of Regeneron Pharmaceuticals, Inc. USA.Legal entity responsible for the studyRegeneron Pharmaceuticals, Inc.FundingRegeneron Pharmaceuticals, Inc.DisclosureM. Mckean: Financial Interests, Institutional, Other, Consulting: Pfizer, Castle Biosciences, IQVIA, Merck, Moderna; Financial Interests, Institutional, Research Grant: Acentage Pharma Group, Bicycle Therapeutics, Dragonfly Therapeutics, Epizyme, Exelixis, Genentech, GSK, IDEAYA Biosciences, Ikena Oncology, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Moderna, NBE Therapeutics, Novartis, Oncorus, Plexxicon, Prelude Therapeutics, Regeneron, Sapience Therapeutics, Seattle Genetics, Tizona Therpeutics, TMUNITY Therapeutics, TopAlliance Biosciences, Aadi Biosciences, Alpine Immune Sciences, Arcs Biosciences, Arvinas, ASCO, Astellas, Bayer, BioMed Valley Discoveries, BioNTech, C4 Therapeutics, EMD Serono, Erasca, Foghorn Therapeutics, G1 Therapeutics, Gilead Sciences, ImmVira Pharma, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, MedImmune, Mereo BioPharma, Metabomed, Nektar, OncoC4, PACT Pharma, Pfizer, Poseida, Pyramid Biosciences, Scholar Rock, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics, Xilio, Aulos Bioscienc, Boehringer Ingelheim Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, InconVir, Jazz Pharmaceutical, Krystal Biotech, NucMito Pharmaceuticals, OnKure, Remix Therapeutics. K.P. Papadopoulos: Financial Interests, Personal, Advisory Board: Turning Point Therapeutics, Bicycle, Basilia; Financial Interests, Institutional, Full or part-time Employment: START; Financial Interests, Personal, Ownership Interest: START; Financial Interests, Institutional, Local PI, For conduct of clinical trial: 3D Medicines, AbbVie, ADC Therapeutics, Amgen, Anheart Therapeutics, Bayer, Daiichi Sankyo, EMD Serono, F-Star, Incyte, Jounce Therapeutics, Lilly, Linnaeus Therapeutics, Merck, Mersana, Mirati Therapeutics, Pfizer, Regeneron Pharmaceuticals, Syros Pharmaceuticals, Tempest Therapeutics, Treadwell Therapeutics, Revolution Medicine, Fog, Sensei, Storm. J.P. Crown: Financial Interests, Personal, Honoraria: Novartis, Pierre Fabre, and Pfizer; Financial Interests, Personal, Advisory roles: AstraZeneca, Immunocore, and MSD Oncology; Financial Interests, Personal, Travel, Accommodation, and Other expenses: AstraZeneca, MSD Oncology, Novartis, Pfizer, Roche, and Regeneron; Financial Interests, Personal, Stock/Shares: Akkure, and Oncoassure; Financial Interests, Personal, Leadership roles: Oncoassure. S. Thomas: Financial Interests, Personal, Honoraria: BMS, Merck, Natera, Springworks, and Pfizer. J.M. Mehnert: Financial Interests, Institutional, Advisory Board, Scientific advisory board: Merck; Financial Interests, Institutional, Advisory Board: Regeneron. J. Kaczmar: Financial Interests, Personal, Advisory Board: PDS Biosciences, EMD Serono; Financial Interests, Institutional, Local PI: EMD, PDS, Bicara, Merck, Replimmune; Financial Interests, Personal, Coordinating PI, research funding for IIT at MUSC: Signatera. K.B. Kim: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Arvinas, Cryoport; Financial Interests, Institutional, Funding, Moderna has provided funding to the institution for conducting a clinical trial of Moderna's drug: Moderna; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Merck, Regeneron, Iovance Biotherapeutics, ImmunoCore, Astex Pharmaceuticals, Ideaya Biosciences, Summit Pharmaceuticals. N.J. Lakhani: Financial Interests, Personal, Advisory Board: Innovent Biologics; Financial Interests, Personal, Advisory Board, Participation in Ad Board: Ikena, SK Life Sciences; Financial Interests, Institutional, Local PI: ALX Therapeutics, Ascentage, Constellation Pharma, Alpine Biosciences, Forty Seven, Merck, Pfizer, Regeneron, Symphogen, InhibRx, Seagen, Sapience Therapeutics, Jounce, Northern Biologics, Odonate, Loxo/Lilly, Ikena, Mersana Therapeutics, Astellas, Celgene, Helsinn, Shattuck Labs, Samumed, GSK, Alkermes, Samumed, Tizona Therapeutics, Gilead, Repare Therapeutics, Alkermes, InhibRx, Janssen, cytomX, KSQ Therapeutics, Repare Therapeutics, Arcus Bio, Artios, Revolution Medicines, Volastra; Financial Interests, Institutional, Coordinating PI: Servier. M.L. Yushak: Financial Interests, Institutional, Local PI: Immunocore, BMS, Merck, Tesaro, X4, Regeneron, Replimune, GSK. J. Mani: Financial Interests, Institutional, Full or part-time Employment: Regeneron Pharmaceuticals; Financial Interests, Institutional, Stocks/Shares: Regeneron Pharmaceuticals. F. Fang: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. L. Brennan: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Eli Lilly, Roche, and Regeneron; Financial Interests, Personal, Research funding, Travel, Accommodation, and Other Expenses with Regeneron; Financial Interests, Personal, Patents, Royalties, and Other Intellectual Property: Eli Lilly. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. M.E. Salvati: Financial Interests, Institutional, Full or part-time Employment, VP Global Program Head, Translational and Clinical Oncology: Regeneron; Financial Interests, Personal, Stocks/Shares, Stocks and options in REGN: Regeneron. M.G. Fury: Financial Interests, Personal, Full or part-time Employment, I am a full-time employee: Regeneron Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, I hold employee stock: Regeneron Pharmaceuticals; Other, Other, My wife is also a full time employee at Regeneron, and holds employee stock: Regeneron Pharmaceuticals. K. Lewis: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, BMS, Bactonix, Beigene, Bioatla, Eisai, GSK, Georgiamune, GigaGen, Grit Bio, IO Biotech, Idera, Immunocore, Incyte, Instil Bio, Iovance, Janssen, KSQ, Merck, Novartis, Obsidian, Pfizer, Roche Genentech, SEAGEN, Sanofi / Regeneron, Tempus, Vial, Zelluna; Financial Interests, Personal, Invited Speaker: BMS, Immunocore, Novartis, Pfizer, Sanofi / Regeneron; Financial Interests, Personal, Stocks/Shares: Bactonix; Financial Interests, Institutional, Local PI: Aduro, Akeso, Amgen, Arcus, BMS, Bioatla, CytomX, Exelixis, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Merck Serono, Moderna, Nextcure, Novartis, Pfizer, Roche Genentech, SEAGEN, Sanofi / Regeneron, Torque, Zelluna. All other authors have declared no conflicts of interest.