LAG-3-blocking antibody relatlimab and nivolumab fixed-dose combination significantly improves progression-free survival vs. Opdivo in patients with previously untreated metastatic or unresectable melanoma.- BMS

Bristol Myers Squibb announced results from the Phase II/III RELATIVITY-047 trial, which showed that the fixed-dose combination of relatlimab, a LAG-3-blocking antibody, and nivolumab, administered as a single infusion, demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit compared to Opdivo (nivolumab) alone in patients with previously untreated metastatic or unresectable melanoma. This is the first regimen to demonstrate a statistical benefit over anti-PD-1 monotherapy in metastatic melanoma . Among patients treated with the combination, the median PFS (mPFS) was significantly longer at 10.12 months (95% Confidence Interval [CI]: 6.37-15.74) vs. 4.63 in those who received Opdivo (95% CI: 3.38–5.62); (Hazard Ratio [HR] 0.75; 95% CI: 0.62-0.92, p=0.0055). The PFS benefit of the fixed-dose combination was observed early, at the time of the first scan, and was consistent over time. In exploratory, descriptive analyses, the combination of relatlimab and nivolumab extended PFS regardless of pre-specified subgroups and stratification factors. These findings (Abstract #9503), the first from a Phase III trial evaluating a LAG-3-blocking antibody, will be presented in an oral abstract session on Sunday, June 6, 2021, from 8:00 a.m. – 11:00 a.m. EDT during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and have been selected for the official ASCO press program. “LAG-3 represents a new immunotherapy target and the results of the RELATIVITY-047 study demonstrated the significant benefit of inhibiting both LAG-3 and PD-1 with the novel combination of relatlimab and nivolumab,” said Dr. F. Stephen Hodi, M.D., director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute. “With the observed efficacy and safety profile, the combination with relatlimab may provide an important new treatment option for patients with metastatic melanoma.” The safety profile of the fixed-dose combination of relatlimab and nivolumab was manageable and consistent with those previously reported for relatlimab and nivolumab. No new safety signals or new types of clinically important events were identified with the fixed-dose combination when compared to Opdivo monotherapy. Grade 3/4 drug-related adverse events were 18.9% in the combination arm compared to 9.7% in the Opdivo arm. Drug-related adverse events leading to discontinuation were 14.6% in the combination arm compared to 6.7% in the Opdivo arm. Lymphocyte-activation gene 3 (LAG-3) and programmed death-1 (PD-1) are two distinct inhibitory immune checkpoints that are often co-expressed on tumor infiltrating lymphocytes (TILs) and contribute to tumor-mediated T-cell exhaustion. Combination therapy with relatlimab, a novel LAG-3-blocking antibody, and nivolumab, a PD-1 inhibitor, enables T-cell activation, leading to the initiation of an improved immune response and promoting tumor cell death.