Abstract 1359TiP
Background
Immune checkpoint inhibitors combined with platinum doublet chemotherapy (PDCT) have improved outcomes for NSCLC; however, some patients with metastatic NSCLC may not benefit from this strategy due to intrinsic or acquired resistance. Lymphocyte-activation gene 3 (LAG-3) is a inhibitory immune checkpoint that is a marker of T-cell exhaustion limiting their activity. RELA is a LAG-3-blocking monoclonal antibody that restores effector function in exhausted T cells. The combination of RELA + NIVO demonstrated superior progression-free survival (PFS) benefit in previously untreated melanoma and was well tolerated with no new safety signals. RELATIVITY-104 will examine the safety and efficacy of first-line RELA + NIVO + PDCT vs. NIVO + PDCT in patients with previously untreated NSCLC.
Trial design
RELATIVITY-104 is a randomized, two-part, phase II study in patients with first-line stage IV or recurrent NSCLC to evaluate the safety profile of RELA + NIVO + PDCT (part 1) and determine if the combination improves PFS compared to NIVO + PDCT (part 2). Patients aged ≥ 18 years must have histologically confirmed stage IV or recurrent NSCLC, an ECOG PS of 0 or 1, and no prior treatment with systemic anticancer therapies for advanced disease. EGFR, ALK, ROS-1, or known BRAFV600E mutations, untreated CNS metastases, or leptomeningeal metastases are exclusion criteria. The primary endpoints are treatment-related adverse events leading to discontinuation within 12 weeks after the first dose (part 1) and PFS per Response Evaluation Criteria In Solid Tumors v 1.1 by blinded independent clinical review (part 2). Secondary endpoints (part 2) include evaluation of the safety and tolerability of RELA + NIVO + PDCT, PFS across biomarker subgroups, and objective response rate. This global study is now enrolling patients.
Clinical trial identification
NCT04623775.
Editorial acknowledgement
Writing and editorial assistance was provided by Ryan Staudt 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
D. Morgensztern: Financial Interests, Personal, Other, Consultant: AbbVie; Financial Interests, Personal, Other, Consultant: G1 Therapeutics; Financial Interests, Personal, Other, Consultant: Takeda; Financial Interests, Personal, Other, Consultant: Gilead; Financial Interests, Personal, Other, Consultant: Boehringer-Ingelheim. A. Chaudhry: Financial Interests, Personal, Stocks/Shares: Novartis; Financial Interests, Personal, Stocks/Shares: Immunomedics. A. Acevedo: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. G. Balaburski: Financial Interests, Personal, Full or part-time Employment: BMS. A. Balogh: Financial Interests, Personal, Full or part-time Employment: BMS. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Mirati, Novartis, PharmaMar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda. Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. All other authors have declared no conflicts of interest.