Imun-05 Phase Ii Study of Nivolumab (Nivo) in Combination With Relatlimab (Rela) in Patients With Active Melanoma Brain Metastases (Mbm)

Abstract BACKGROUND More than half of patients diagnosed with metastatic melanoma (MM) will develop brain metastases. Despite this prevalence, these patients are excluded from most clinical trials. The CheckMate 204 study combining ipilimumab (3mg/kg) plus nivo (1mg/kg) for patients with asymptomatic MBM revealed an intracranial (IC) response in 54% of patients. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 55% of patients. RELATIVITY-047, a global phase II/III randomized study, reported on the fixed-dose combination of nivo/rela (480 mg/160 mg) compared to nivo (480 mg) alone for patients with advanced unresectable and untreated melanoma. This combination demonstrated significantly improved PFS compared to anti-PD-1 monotherapy. Grade 3/4 TRAEs occurred in 21% of patients in the combination group compared to 11% in the monotherapy group with no new safety signals. The nivo/rela combination has FDA approval for the treatment of patients with MM but has not been studied in patients with MBM. METHODS This single arm, single center phase II trial evaluates the safety and efficacy of nivo/rela in patients with MBM. 30 MBM patients who are asymptomatic and treatment naïve to anti-PD-1 therapy will be enrolled. Patients are treated with nivo/rela (480 mg/160 mg) every 4 weeks for up to 25 cycles, disease progression, or unacceptable toxicity. The primary objective is to evaluate IC response (CR + PR) by MRI per modified RECIST 1.1 criteria. Monitoring for futility will be performed using the Bayesian Optimal Phase 2 design. Longitudinal research blood, tissue, and microbiome samples will be collected along with neurocognitive assessments and quality of life surveys. RESULTS This study is actively enrolling. Eight of planned 30 subjects have been treated. At a median follow-up of 8 months, IC response was seen in 43% of patients. Grade 3 TRAEs occurred in 12% of patients with no new safety signals.