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

Abstract

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