P-61 Relatlimab + nivolumab in patients with advanced hepatocellular carcinoma who are naive to immuno-oncology therapy but progressed on tyrosine kinase inhibitors, a phase 2, randomized, open-label study: RELATIVITY-073

Immuno-oncology (IO) therapies, used alone or in combination, have improved outcomes advanced hepatocellular carcinoma (HCC); however, not all patients benefit and novel IO combinations are needed to further enhance the benefit-risk profile. Lymphocyte-activation gene 3 (LAG-3) regulates an inhibitory immune checkpoint pathway, limiting T-cell activity, is a marker for exhaustion resistance therapies. LAG-3 upregulated many tumors including HCC. Relatlimab (RELA), LAG-3-blocking antibody, restores effector function of exhausted T cells. Nivolumab (NIVO) programmed death-1 (PD-1)-blocking antibody approved second-line treatment Preclinical data indicate that dual inhibition PD-1 pathways with RELA + NIVO, respectively, may leverage potentially synergistic enable activation improve response. RELATIVITY-073 will evaluate preliminary efficacy safety NIVO previously treated IO-naive open-label, randomized, phase 2 study HCC who progressed on prior tyrosine kinase inhibitor therapy advanced/metastatic setting. Patients aged ≥ 18 years must histologically confirmed, any etiology, eligible curative surgical and/or locoregional therapy, Child-Pugh score 5 6, ECOG performance status 0 1. Tumor tissue be provided biomarker analysis evaluable tumor expression randomization. active brain metastases leptomeningeal metastases, uncontrolled significant cardiovascular disease, clinically ascites excluded. Approximately 250 randomized 2:1:2 (treatment arm A) one two regimens arms B C) assess different dose levels. The primary endpoint objective response rate (ORR) per RECIST v1.1 as assessed by blinded independent central review. Other endpoints include tolerability, disease control rate, duration response, progression-free survival, overall dose-response relationship using best ORR status. This enrolling globally. NCT04567615. All authors contributed abstract; writing editorial assistance was Kathryn Woods Adam Paton Complete HealthVizion, funded Bristol Myers Squibb.