1036O - Relatlimab (RELA) + nivolumab (NIVO) vs. NIVO in previously untreated metastatic or unresectable melanoma: Additional efficacy in RELATIVITY-047

Background

RELATIVITY-047 (NCT03470922) evaluated RELA (a LAG-3-blocking antibody) + NIVO as a fixed-dose combination (FDC) vs NIVO in pts with advanced melanoma. The FDC demonstrated superior progression-free survival (PFS) by blinded independent central review in the intent-to-treat (ITT) population with a well-tolerated safety profile and no unexpected safety signals. In this exploratory analysis, we describe the potential benefit in subgroups and beyond initial treatment.

Methods

Pts in RELATIVITY-047 were randomized 1:1 to RELA 160 mg + NIVO 480 mg FDC or NIVO monotherapy 480 mg intravenously every 4 weeks. Treatment continued until progression, unacceptable toxicity, or withdrawal of consent. PFS was assessed across subgroups. PFS2 was defined as the time from randomization to progression on subsequent therapy or death per investigator assessment. Treatment-free time from last study dose to subsequent therapy was also assessed.

Results

714 pts were randomized to RELA + NIVO FDC (n = 355) or NIVO (n = 359). RELA + NIVO FDC extended PFS across prespecified subgroups, including BRAF, AJCC v8 M stage, and LDH. Median treatment duration was 5.6 mo for RELA + NIVO FDC and 4.9 mo for NIVO and 237 (66.8%) and 233 pts (64.9%), respectively, discontinued treatment, mainly due to disease progression (36.3% vs 46.0%). Pts receiving subsequent systemic therapy in RELA + NIVO FDC and NIVO were 27.9% and 29.8%, respectively, including PD-1 or CTLA-4 inhibitors (9.0% vs 12.8%) and BRAF/MEK therapies (11.5% vs 13.9%). PFS2 favored RELA + NIVO FDC with a median not reached (95% CI 21.8–NA) vs 20.0 mo (95% CI 15.4–25.1) for NIVO (hazard ratio [HR] 0.77 [95% CI 0.61–0.97]). Median treatment-free time from last study dose to subsequent therapy was 3.98 mo (95% CI 2.10–7.43) for RELA + NIVO FDC vs 1.45 mo (95% CI 1.25–1.71) for NIVO (HR 0.63 [95% CI 0.48–0.83]).

Conclusions

RELA + NIVO FDC had demonstrated prolonged PFS in ITT and subgroups of pts with previously untreated metastatic or unresectable melanoma. Pts on RELA + NIVO FDC had enduring benefit beyond initial treatment and prolonged benefit beyond first progression, including longer time to initiation of subsequent treatment.

Clinical trial identification

NCT03470922.

Editorial acknowledgement

Editorial assistance was provided by Amy Graham and Adam Paton of Complete HealthVizion, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

F..S. Hodi: Financial Interests, Personal and Institutional, Other, Consultant; clinical trial support to institution: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Other, Consultant; clinical trial support to institution: Merck; Financial Interests, Personal and Institutional, Other, Consultant; clinical trial support to institution: Novartis; Financial Interests, Personal and Institutional, Other, Consultant: EMD Serono; Financial Interests, Personal and Institutional, Other, Consultant; clinical trial support to institution: Sanofi; Financial Interests, Personal, Other, Board member; shares: Apricity; Financial Interests, Personal, Other, Board member; shares: Bicara; Financial Interests, Personal, Other, Consulting; equity: Pionyr; Financial Interests, Personal, Other, Consulting: Surface; Financial Interests, Personal, Other, Consulting; equity: Compass; Financial Interests, Personal, Other, Consulting: Aduro; Financial Interests, Personal, Other, Consulting: Torque; Financial Interests, Personal, Other, Consulting: Checkpoint Therapeutics; Financial Interests, Personal, Other, Consulting: Idera; Financial Interests, Personal, Other, Consulting: Takeda; Financial Interests, Personal, Other, Consulting: Bioentre; Financial Interests, Personal, Other, Consulting: Gossamer; Financial Interests, Personal, Other, Consulting: Iovance; Financial Interests, Personal, Other, Consulting: Trillium; Financial Interests, Personal, Other, Consulting: Millenium. H.A. Tawbi: Financial Interests, Personal, Other, Consulting fees: BMS; Financial Interests, Personal, Other, Consulting fees: Merck; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Other, Consulting fees: Genentech; Financial Interests, Personal, Other, Consulting fees: Eisai; Financial Interests, Personal, Other, Consulting fees: Lovance; Financial Interests, Personal, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: GSK. E.J. Lipson: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Array BioPharma; Financial Interests, Personal, Other, Consultant: Macrogenics; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Odonate Therapeutics; Non-Financial Interests, Institutional, Other, Coordinating PI: Bristol-Myers Squibb; Non-Financial Interests, Institutional, Other, Local PI: Regeneron; Non-Financial Interests, Institutional, Other, Local PI: Merck. D. Schadendorf: Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Array Bipharma; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: NEKTAR; Financial Interests, Personal, Advisory Board: Neracare; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philogen; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi/Regeneron; Financial Interests, Personal, Other, Steering Committee Member: 4SC; Non-Financial Interests, Institutional, Invited Speaker, Coordinating PI: 4SC; Financial Interests, Institutional, Research Grant: Array/Pfizer; Non-Financial Interests, Institutional, Other, Coordinating PI: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Other, Steering Committee Member: Bristol-Myers Squibb; Financial Interests, Personal, Other, Steering Committee Member: MSD; Non-Financial Interests, Institutional, Other, Coordinating PI: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Other, Steering Committee Member: Nektar; Non-Financial Interests, Institutional, Other, Coordinating PI: Nektar; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Steering Committee Member: Novartis; Non-Financial Interests, Institutional, Other, Coordinating PI: Novartis; Non-Financial Interests, Institutional, Other, Local PI: Philogen; Non-Financial Interests, Institutional, Other, Coordinating PI: Pierre Fabre; Non-Financial Interests, Institutional, Other, Local PI: Roche; Non-Financial Interests, Institutional, Other, Local PI: Sanofi; Non-Financial Interests, Personal, Member of the Board of Directors: EORTC-MG. P.A. Ascierto: Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Roche-Genentech; Financial Interests, Institutional, Advisory Role: MSD; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Array; Financial Interests, Institutional, Advisory Role: Merck Serono; Financial Interests, Institutional, Advisory Role: Pierre Fabre; Financial Interests, Institutional, Advisory Role: Incyte; Financial Interests, Institutional, Advisory Role: Newlinks Genetics; Financial Interests, Institutional, Advisory Role: Genmab; Financial Interests, Institutional, Advisory Role: Medimmune; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Sindax; Financial Interests, Institutional, Advisory Role: Sun Pharma; Financial Interests, Institutional, Advisory Role: Sanofi; Financial Interests, Institutional, Advisory Role: Idera; Financial Interests, Institutional, Advisory Role: Ultimovacs; Financial Interests, Institutional, Advisory Role: Sandoz; Financial Interests, Institutional, Advisory Role: Immunocore; Financial Interests, Institutional, Advisory Role: 4SC. L. Matamala: Financial Interests, Institutional, Full or part-time Employment: Fundacion Arturo Lopez Perez. E.C. Gutiérrez: Non-Financial Interests, Institutional, Principal Investigator: FAICIC S de RL de CV. P. Rutkowski: Financial Interests, Personal, Advisory Board: Blueprint Medicines; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Other, Officer: ASCO; Non-Financial Interests, Institutional, Member of the Board of Directors: Polish Society of Surgical Oncology. H.J. Gogas: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Non-Financial Interests, Personal, Other, Steering Committee Member: Amgen; Financial Interests, Institutional, Other, Local PI: Amgen; Financial Interests, Institutional, Research Grant, Bristol-Myers Squibb: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Local PI: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Local PI: MSD; Financial Interests, Institutional, Research Grant: Pfizer. C.D. Lao: Financial Interests, Personal and Institutional, Sponsor/Funding: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Sponsor/Funding: Novartis. S. Dalle: Financial Interests, Institutional, Advisory Board: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant, Bristol-Myers Squibb: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: MSD. A. Arance: Financial Interests, Personal, Other: Consultant, Advisor, Speaker, Travel and Accomodations Expenses, Research Funding: Pierre Fabre; Financial Interests, Personal, Other: Consultant, Advisory, Speaker, Travel and Accomodations, Expenses, Research Funding: Novartis; Financial Interests, Personal, Other, Consultant, Advisor, Speaker, Travel and Accomodations- Expenses, Research Funding: Roche; Financial Interests, Personal, Other: Consultant, Advisor, Speaker, Travel and Accomodations- Expenses, Research Funding: BMS; Financial Interests, Personal, Other: Consultant, Advisor, Speaker, Travel and Accomodations- Expenses, Research Funding: MSD; Financial Interests, Personal, Other: Consultant, Advisory, Speaker, Travel and Accomodations Expenses, Research Funding: Merck; Financial Interests, Personal, Other,. Consultant, Advisory, Speaker, Travel and Accomodations- Expenses, Research Funding: Sanofi; Financial Interests, Personal, Other: Consultant, Advisory, Speaker, Travel and Accomodations Expenses, Research Funding: Amgen. J.J. Grob: Financial Interests, Personal and Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Advisory Role: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Advisory Role: Pierre Fabre; Financial Interests, Personal and Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Personal and Institutional, Advisory Role: Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Amgen; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Sunpharma; Financial Interests, Personal and Institutional, Invited Speaker: Sunpharma; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Advisory Board: Philogen. L. Toms: Financial Interests, Personal, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol-Myers Squibb. K. Jonczak: Financial Interests, Institutional, Full or part-time Employment: Bristol-Myers Squibb. A.M. Sobiesk: Financial Interests, Personal and Institutional, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Stocks/Shares: Bristol-Myers Squibb. G.V. Long: Financial Interests, Personal, Advisory Role: Aduro Biotech Inc; Financial Interests, Personal, Advisory Board: Aduro Biotech Inc; Financial Interests, Personal, Advisory Role: Amgen Inc; Financial Interests, Personal, Advisory Board: Amgen Inc; Financial Interests, Personal, Advisory Role: Array Biopharma inc; Financial Interests, Personal, Advisory Board: Array Biopharma inc; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim Int GmbH; Financial Interests, Personal, Advisory Board, Bristol-Myers Squibb: Boehringer Ingelheim Int GmbH; Financial Interests, Personal, Advisory Role, Bristol-Myers Squibb: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Hexel AG; Financial Interests, Personal, Advisory Board: Hexel AG; Financial Interests, Personal, Advisory Role: Highlight Therapeutics S.L.; Financial Interests, Personal, Advisory Board: Highlight Therapeutics S.L.; Financial Interests, Personal, Advisory Role: Merck Sharpe & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharpe & Dohme; Financial Interests, Personal, Advisory Role: Novartis Pharma AG; Financial Interests, Personal, Advisory Board: Novartis Pharma AG; Financial Interests, Personal, Advisory Role: OncoSec; Financial Interests, Personal, Advisory Board: OncoSec; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Role: QBiotics Group Limited; Financial Interests, Personal, Advisory Board: QBiotics Group Limited; Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board: Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Role: Specialised Therapeutics Australia Pty Ltd.; Financial Interests, Personal, Advisory Board, Bristol-Myers Squibb: Specialised Therapeutics Australia Pty Ltd.; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Pierre Fabre. All other authors have declared no conflicts of interest.