LBA53 - Nivolumab (NIVO) plus relatlimab with platinum-doublet chemotherapy (PDCT) vs NIVO + PDCT as first-line (1L) treatment (tx) for stage IV or recurrent NSCLC: Results from the randomized phase II RELATIVITY-104 study

Background

PD-1 and LAG-3 (immune checkpoints upregulated in NSCLC) inhibit effector T-cell function and promote T-cell dysfunction. NIVO 480 mg + relatlimab (RELA, a human LAG-3–blocking antibody) 160 mg Q4W significantly improved PFS vs NIVO in advanced melanoma, leading to regulatory approval. Here we report results from RELATIVITY-104, the first randomized phase 2 study assessing a LAG-3–blocking antibody-containing regimen as 1L tx for metastatic NSCLC.

Methods

Adults with previously untreated stage IV/recurrent NSCLC, ECOG PS ≤ 1, and no targetable mutations were eligible. Part 1 evaluated the safety of NIVO 360 mg + RELA 360 mg/720 mg + PDCT Q3W. In Part 2, pts were randomized 1:1 (stratified by PD-L1 expression, histology, ECOG PS) to NIVO 360 mg + RELA 360 mg + PDCT or NIVO 360 mg + PDCT Q3W; ORR per BICR was the primary endpoint. Secondary endpoints included PFS per BICR, ORR/PFS by biomarker subgroups, and safety.

Results

In Part 1 (n = 159), safety and efficacy of NIVO + RELA (both doses) + PDCT were demonstrated. In Part 2 (n = 309; median follow-up: 10.7 mo), ORR favored NIVO + RELA 360 mg + PDCT (51.3%) vs NIVO + PDCT (43.7%); mDOR (90% CI) was 10.1 mo (7.4–not reached [NR]) vs 9.1 mo (6.7–13.4); PFS HR (90% CI) was 0.88 (0.71–1.11). ORR and PFS benefit were seen in pre-specified subgroups (eg, PD-L1 ≥ 1%, NSQ histology). OS data are immature. NIVO + RELA 360 mg + PDCT displayed a manageable safety profile; rates of grade 3–4 TRAEs were 54% vs 55% and TRAEs leading to death were 3.8% vs 3.4% for NIVO + RELA 360 mg + PDCT vs NIVO + PDCT in Part 2.

Conclusions

In this head-to-head proof-of-concept phase 2 study, NIVO + RELA 360 mg + PDCT demonstrated improved clinical benefit vs NIVO + PDCT, particularly in PD-L1 ≥ 1% and NSQ pre-specified subgroups. Further phase 3 investigation is warranted. Table: LBA53

^a(90% CI)^bPart 1 RELA 360mg dose in PD-L1 ≥ 1% & NSQ (n = 22): mPFS 10.9 mo, ORR 50.0%.

Clinical trial identification

NCT04623775.

Editorial acknowledgement

Writing and editorial assistance were provided by Chandre Sammy, PhD, Samantha L. Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. M. Burotto: Financial Interests, Personal, Invited Speaker: BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Merck. L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag international NV, NOvartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President. ASEICA (Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi, GSK, Pfizer; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi, GSK, Lilly; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Amgen, Boehringer Ingelheim, BeiGene, Daiichi Sankyo, GSK, BMS, Lilly, MSD, Regeneron, Roche; Financial Interests, Institutional, Local PI: Pfizer Seagen. M. Schenker: Financial Interests, Personal and Institutional, Local PI, Payment for Clinical trials activities: B.M.S., M.S.D., Roche, Merck Serono, Sanofi, Regeneron, AstraZeneca, Pfizer, G.S.K, Novartis, Astellas, Pharma Mar, BeiGene, Clovis Pharmaceutical, AbbVie, Bioven, Mylan, Samsung Pharmaceutical, Eisai, Gilead, Amgen, Daiichi Sankyo. J. Naidoo: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Roche/Genentech, Bristol Myers Squibb, Takeda, Pfizer, Amgen, NGM Pharmaceuticals, Kaleido Biosciences, AbbVie, Elevation Oncology, Regeneron; Financial Interests, Personal, Other, independent adjudication of adverse events: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Merck, Novartis, Bristol Myers Squibb, Pfizer, Roche/Genentech; Financial Interests, Institutional, Local PI: Mirati. E.K. Beardlsey: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, MSD, Ipsen. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. P. Kasbekar: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. M. Chowdhury: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. A. Tendolkar: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. All other authors have declared no conflicts of interest.