NEW YORK – The European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP) on Friday recommended Bristol Myers Squibb's Opdualag (nivolumab plus relatlimab) for approval in Europe as a first-line treatment for advanced melanoma patients whose tumors express PD-L1 in fewer than one percent of cells.
The European Commission will now review CHMP's opinion and decide whether to make the immunotherapy combination commercially available across the European Union.
The committee's recommendation is based on the results of the Phase II/III RELATIVITY-047 clinical trial, in which a fixed-dose combination of BMS's PD-1 inhibitor Opdivo (nivolumab) and LAG-3 inhibitor relatlimab — now dubbed Opdualag when combined — more than doubled progression-free survival compared to Opdivo alone in all patients regardless of PD-L1 expression. In a prespecified exploratory analysis, patients with PD-L1 expression of one percent or greater had similar progression-free survival outcomes on the Opdivo and Opdualag arms, whereas the patients with PD-L1 expression of less than one percent had a median progression-free survival of 6.4 months with Opdualag versus 2.9 months with Opdivo alone.
Despite the greater degree of benefit in the lower-PD-L1-expressing biomarker subgroup, the US Food and Drug Administration in March approved Opdualag for advanced melanoma patients regardless of PD-L1 expression. CHMP, in contrast, has recommended Opdualag's approval in a narrower, biomarker-defined indication based on the exploratory analysis.
Given that inhibiting LAG-3 is expected to restore immune responses, including in patients who don't respond to Opdivo alone, BMS is evaluating Opdualag in a variety of tumor types, including in cancers with mismatch repair-deficiency and high microsatellite instability, as well as in LAG-3- and PD-L1-expressing tumors.