Real-world efficacy of relatlimab and nivolumab in advanced or resectable melanoma

BackgroundFixed-dose combination NIV-RELA improves progression-free survival (PFS) compared to NIV in patients (pts) with therapy-naive advanced melanoma (MEL) (10.1m vs. 4.6m) but has limited activity after prior immunotherapy. The pathologic response rate (pathRR) to neoadjuvant NIV-RELA is 70%. Real-world data on safety & efficacy of NIV-RELA is lacking. We report the largest single center experience of NIV-RELA in advanced MEL & as neoadjuvant therapy in resectable MEL.MethodsAll MEL pts treated with NIV-RELA from FDA approval until 3/2024 were grouped in 3 cohorts (C): 1st line (C1, n=68) or subsequent line (C2, n=120) advanced MEL & neoadjuvant (C3, n=17). Safety, PFS, overall survival (OS) & pathRR in relation to MEL characteristics were evaluated.ResultsThe table shows demographic and efficacy data. In C1, pts with ≥3 vs. <3 organs involved had worse PFS (p= 0.007); normal LDH vs. > upper level of normal (ULN) LDH pts had improved PFS (p=0.04). For C2 pts, ≥3 vs. <3 organs involved had worse OS (p=0.02); normal LDH vs. >ULN LDH and ECOG 0 vs. ECOG ≥1 had improved OS (p<0.001). In pts with prior anti-PD1 only (22%), the mPFS & mOS were 5.8m (3.4-NR) & 17m (12-NR) respectively. Adverse events (AEs) occurring in ≥5% C1 pts were dermatologic (40%), arthralgia (19%), colitis (10%), adrenal insufficiency (AI, 9%) & transaminitis (9%). In C2, AEs in ≥5% pts were dermatologic (18%), arthralgia (7.5%), colitis (5%) & transaminitis (5%). In 16 evaluable C3 pts, 3 had clinical progression, 2 partial & 6 pathologic non-response. PathRR was 44%, all in BRAF WT MEL. No pathologic responder has recurred. AEs in ≥10% of C3 pts were dermatologic (35%), AI (12%), myocarditis (12%) & transaminitis (12%). Table: 1103P Cohort 1(n=68) Cohort 2(n=120) Cohort 3(n=17) Median follow-up 9.1m 11m 8.4m Median age 70y 68y 65y Female % 32 33 47 BRAF WT 34/57 72/117 12/17 Normal LDH 51/62 79/113 15/16 Liver mets % 10 28 0 ≥3 organs involved % 13 34 0 mPFS 19m (7.3-NR) 3m (2.7-3.9) NA 6m PFS/OS % 64/ 92 30 / 71 NA/100 mOS NR 14m (9.7-19) NR 12m PFS/OS % 57 / 83 14 / 56 NA/100 Major Pathologic Response Rate % NA NA 31 Pathologic Complete/Near-Complete response NA NA 3/2 TRAEs-requiring steroid therapy % 56 38 41 ConclusionsCombination Our cohort confirms 1st-line efficacy of NIV-RELA in advanced MEL but with high rate of steroid-requiring AEs. For subsequent lines, pts with prior anti-PD1 only may derive greater benefit. In resectable MEL, the pathRR appears lower than previously reported.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureZ. Eroglu: Financial Interests, Personal, Advisory Board: Pfizer, Regeneron, SunPharma, Incyte; Non-Financial Interests, Institutional, Research Funding: Pfizer, Novartis, Boehringer Ingelheim-Ingelheim. J. Markowitz: Non-Financial Interests, Personal, Research Funding: Merck, Morphogenesis, Microba. A. Tarhini: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck, Genetech/Roche, Sanofi/Regeneron, Novartis, Partner Therapeutics; Non-Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Merck, Genetech/Roche, Sanofit/Regeneron; Financial Interests, Personal, Advisory Board: Eisai, Bayer, Instil Bio, ConcertAI, BioNTech; Financial Interests, Institutional, Funding: OncoSec (Inst), Sanofi/Regeneron (Inst), Clinigen Group (Inst), InflaRx (Inst), Acrotech Biopharma (Inst), Pfizer (Inst), Agenus (Inst), Scholar Rock (Inst). J. Messina: Non-Financial Interests, Leadership Role, Co-chair two committees: Fellowship Director's Committee and Program Committee: American Society of Dermatopathology. K.Y. Tsai: Financial Interests, Personal, Advisory Board: NFlection Therapeutics; Financial Interests, Personal, Other, Consultant: Verrica Pharmaceuticals; Financial Interests, Institutional, Full or part-time Employment: Moffitt Cancer Center; Financial Interests, Personal, Stocks/Shares: 3CC, NFlection Therapeutics; Financial Interests, Institutional, Research Grant: Incyte; Non-Financial Interests, Member: ASCO. J.S. Zager: Financial Interests, Personal, Invited Speaker: Merit Medical; Financial Interests, Personal, Advisory Board: Delcath Systems, Merck, Philogen; Financial Interests, Institutional, Research Grant: Delcath Systems; Financial Interests, Institutional, Local PI: Provectus; Financial Interests, Institutional, Coordinating PI: Philogen. A. Sarnaik: Financial Interests, Institutional, Other, Sponsored research and Institutional patent licensed: Iovance Biotherapeutics; Financial Interests, Personal, Other, Consultant: Gerson Lehrman Group; Financial Interests, Personal, Other, consultant: Guidepoint; Financial Interests, Personal, Invited Speaker: international workshop CAR-T, Society for the Immunotherapy of Cancer, Blueprint Oncology Concepts, Second City Science, MJH Holdings; Financial Interests, Institutional, Other, Sponsored Research: Turnstone Biologics Inc; Financial Interests, Personal, Other, Sponsored research and personal patent: Provectus Biopharmaceuticals; Financial Interests, Institutional, Advisory Board, My institution has licensed intellectual property to Iovance Biotherapeutics: Iovance Biotherapeutics; Financial Interests, Personal, Other, I am a co-inventor on a patent application with Provectus Biopharmaceuticals that could provide an income in the future: Provectus; Financial Interests, Personal and Institutional, Trial Chair: Iovance Biotherapeutics; Financial Interests, Institutional, Local PI: Provectus Biotherapeutics, Turnstone Biologics; Non-Financial Interests, Principal Investigator: Turnstone Biologics, Iovance Biotherapeutics. V. Sondak: Financial Interests, Personal, Advisory Board: Merck, Bristol Myers Squibb, Iovance, OncoSec, Regeneron, Ultimovacs; Financial Interests, Personal, Other, Independent Data Safety Monitoring Committee: Alkermes, Novartis; Financial Interests, Personal, Other, Independent medical monitor for clinical trial: Genesis Drug Discovery & Development; Financial Interests, Institutional, Research Grant, Research grant to institution: Turnstone Biologics; Financial Interests, Institutional, Coordinating PI, Per patient funding to institution to support clinical trial: Skyline DX; Financial Interests, Institutional, Local PI, Research grant to institution: Neogene Therapeutics. N.I. Khushalani: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Bristol Myers Squibb, AstraZeneca, Regeneron, Array BioPharma, Immunocore, Merck, Incyte, Jounce Therapeutics, Iovance Biotherapeutics, NCCN/Pfizer, Genzyme, Novartis, Nektar, Castle Biosciences and Instil Bio. All other authors have declared no conflicts of interest.