817P - Nivolumab (NIVO) + relatlimab (RELA) vs NIVO in previously untreated metastatic or unresectable melanoma: Additional response outcomes from RELATIVITY-047

Background

In the phase 2/3 RELATIVITY-047 trial, NIVO + RELA as a fixed-dose combination (FDC) significantly improved the primary endpoint of progression-free survival (PFS) and showed a clinically meaningful improvement in overall survival (OS), although not statistically significant, with a numerically higher confirmed objective response rate (ORR) vs NIVO in patients (pts) with previously untreated metastatic or unresectable melanoma. NIVO + RELA had a manageable safety profile with no new or unexpected safety signals. Here, we report additional response outcomes.

Methods

Pts were randomized 1:1 to NIVO 480 mg + RELA 160 mg FDC or NIVO 480 mg intravenously every 4 weeks. The primary endpoint of PFS per RECIST v1.1 was assessed by blinded independent central review (BICR). Secondary endpoints, to be tested in hierarchy, were OS and then ORR by BICR. Exploratory analyses were performed to further characterize tumor responses and associated outcomes.

Results

Pts received NIVO + RELA (n = 355) or NIVO (n = 359). Median follow-up was 19.3 months (mo). Confirmed ORR by BICR was 43.1% vs 32.6% and median time (range) to objective response was 2.8 mo (1.2–12.2 mo) vs 2.8 mo (1.7–20.1 mo) with NIVO + RELA vs NIVO, respectively. Among pts with an objective response, 88% responded within 20 weeks (second imaging scan) on NIVO + RELA vs 82% on NIVO. Median duration of response (DOR) was not reached in either arm. Among responders, the proportion of pts with a DOR of at least 12 (80% vs 85%) and 18 mo (75% vs 73%) was similar with NIVO + RELA vs NIVO, respectively. In both arms, PFS and OS were greater in responders vs nonresponders (Table). PFS and OS Kaplan-Meier curves by response will be presented.

Conclusions

Durable responses occurred in patients treated with either NIVO + RELA or NIVO, with numerically higher response rates for NIVO + RELA vs NIVO. In both arms, pts who responded to treatment had substantially improved PFS and OS vs nonresponders. Table: 817P

Responder: complete or partial response; Nonresponder: stable disease, progressive disease, noncomplete response or nonprogressive disease.CI, confidence interval; NR, not reached.

Clinical trial identification

NCT03470922.

Editorial acknowledgement

All authors contributed to, and approved, the abstract; writing and editorial assistance were provided by Jenifer Li, Adam Paton, and Jane Beck of Complete HealthVizion, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

This study is supported by Bristol Myers Squibb (Princeton, NJ, USA).

Disclosure

F.S. Hodi: Financial Interests, Personal, Advisory Board: Merck, Novartis, Genentech, EMD Serono, Sanofi, Amgen, Surface, Compass, Pionyr, Checkpoint Therapeutics, Bioentre, Gossamer, Iovance, Immunocore, Trillium, Catalym, Kairos, Eisai, Corner Therapeutics, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Board: Apricity; Financial Interests, Personal, Other, Board: Bicara; Financial Interests, Personal, Invited Speaker: Bicara, Apricity; Financial Interests, Personal, Stocks/Shares: Bicara, Apricity, Pionyr; Financial Interests, Institutional, Invited Speaker, To institution per institutional policies personal distribution: Novartis; Financial Interests, Institutional, Invited Speaker, o institution per institutional policies personal distribution: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Novartis, Genentech, Merck, Incyte, Boehringer Ingelheim, Merus. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Merck, Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. E.J. Lipson: Financial Interests, Personal, Advisory Board: Bristol Myers-Squibb, Merck, Sanofi, Regeneron, Genentech, Odonate Therapeutics, Eisai, Instil Bio, Natera, Nektar Therapeutics, Pfizer, Rain Therapeutics; Financial Interests, Personal, Other, Consultant: Macrogenics, OncoSec; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Regeneron, Merck. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi, Merck, Novartis, BMS, MSD, 4SC, Nektar; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Roche, Merck Serono, Immunocore, 4SC, Pierre Fabre, Sanofi/Regeneron, Array Biopharma, Pfizer, Philogen, Nektar, Sandoz, Neracare; Financial Interests, Institutional, Research Grant: Novartis, BMS, MSD, Array/Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis, BMS, MSD, Pierre Fabre, Sanofi, Roche, Philogen, 4SC, Nektar; Non-Financial Interests, Invited Speaker: EORTC-MG. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: Dohme, iTeos; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. L.A. Matamala: Financial Interests, Institutional, Full or part-time Employment, Medical Oncologist: Fundacion Arturo Lopez Perez. P. Salman: Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis, MSD, BMS, AstraZeneca. E.C. Gutierrez: Non-Financial Interests, Institutional, Principal Investigator: FAICIC S de RL de CV. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, Officer: ASCO; Non-Financial Interests, Invited Speaker, President Elect: Polish Oncological Society. H.J. Gogas: Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Pierre Fabre, SANOFI; Financial Interests, Invited Speaker: Amgen, Replimune; Financial Interests, Institutional, Invited Speaker: Amgen, MSD, BMS, Replimune, Iovance; Financial Interests, Institutional, Research Grant: BMS, Pfizer. C.D. Lao: Financial Interests, Institutional, Invited Speaker, Research funding: BMS, Novartis, Genentech, Oncosec. J. Menezes: Non-Financial Interests, Personal, Advisory Board, Participating in advisory board: Bristol Myers Squibb. S. Dalle: Financial Interests, Institutional, Advisory Board: MSD, BMS; Financial Interests, Institutional, Research Grant: BMS, MSD. A.M. Arance Fernandez: Financial Interests, Personal, Advisory Board, Consultant /Advisory/ Speaker / Travel, Accomodations, Expenses/: Pierre Fabre, Novartis, Roche, BMS, MSD, Merck, Sanofi; Financial Interests, Institutional, Other, Research Funding: Pierre Fabre, Novartis, MSD, BMS, Merck, Roche, Sanofi, Amgem. J.J. Grob: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Roche, Pierre Fabre, Novartis, Pfizer, Sanofi, Philogen, Iteos Therapeutics, Sunpharma; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Pierre Fabre, Sanofi, Novartis; Financial Interests, Institutional, Research Grant: Pierre Fabre. S. Keidel: Financial Interests, Personal, Full or part-time Employment, Full time employee of BMS including receiving shares: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares, Share ownership: Bristol Myers Squibb. S. Rodriguez: Financial Interests, Personal, Full or part-time Employment, I am employed by Bristol Myers Squibb as a Senior Clinical Scientist: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares, I am a stock/shares owner of Bristol Myers Squibb: Bristol Myers Squibb. S. Dolfi: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. All other authors have declared no conflicts of interest.