LAG-3 inhibitor plus PD-1 inhibitor

A multinational, phase II/III, double-blind trial (RELATIVITY-047 [NCT03470922]) included 714 patients with previously untreated, histologically confirmed, unresectable stage III or IV melanoma. Patients were randomly assigned in a 1:1 ratio to receive either 160 mg of relatlimab and 480 mg of nivolumab in a fixed-dose combination (n = 355) or 480 mg of nivolumab (n = 359). The characteristics of the patients at baseline were well balanced between the treatment groups. Both therapies were given in a single 60-minute IV infusion every 4 weeks. The primary end point was PFS assessed according to RECIST, version 1.1. Secondary end points included OS and objective response. Patients who had received previous adjuvant or neoadjuvant therapies containing a PD-1, CTLA-4, BRAF, or MEK inhibitor (or a combination of BRAF and MEK inhibitors) were eligible if the therapy was completed at least 6 months before the date of recurrence. Key exclusion criteria were uveal melanoma and active, untreated brain or leptomeningeal metastases.[16]

A multinational, phase II/III, double-blind trial (RELATIVITY-047 [NCT03470922]) included 714 patients with previously untreated, histologically confirmed, unresectable stage III or IV melanoma. Patients were randomly assigned in a 1:1 ratio to receive either 160 mg of relatlimab and 480 mg of nivolumab in a fixed-dose combination (n = 355) or 480 mg of nivolumab (n = 359). The characteristics of the patients at baseline were well balanced between the treatment groups. Both therapies were given in a single 60-minute IV infusion every 4 weeks. The primary end point was PFS assessed according to RECIST, version 1.1. Secondary end points included OS and objective response. Patients who had received previous adjuvant or neoadjuvant therapies containing a PD-1, CTLA-4, BRAF, or MEK inhibitor (or a combination of BRAF and MEK inhibitors) were eligible if the therapy was completed at least 6 months before the date of recurrence. Key exclusion criteria were uveal melanoma and active, untreated brain or leptomeningeal metastases.[16]

The median PFS was 10.1 months (95% CI, 6.4–15.7) in the relatlimab-nivolumab group and 4.6 months (95% CI, 3.4–5.6) in the nivolumab-alone group (HRprogression or death, 0.75; 95% CI, 0.62–0.92; P = .006). The 12-month PFS rate was 47.7% (95% CI, 41.8%–53.2%) in the relatlimab-nivolumab group and 36.0% (95% CI, 30.5%–41.6%) in the nivolumab-alone group.[16][Level of evidence B1]

A multinational, phase II/III, double-blind trial (RELATIVITY-047 [NCT03470922]) included 714 patients with previously untreated, histologically confirmed, unresectable stage III or IV melanoma. Patients were randomly assigned in a 1:1 ratio to receive either 160 mg of relatlimab and 480 mg of nivolumab in a fixed-dose combination (n = 355) or 480 mg of nivolumab (n = 359). The characteristics of the patients at baseline were well balanced between the treatment groups. Both therapies were given in a single 60-minute IV infusion every 4 weeks. The primary end point was PFS assessed according to RECIST, version 1.1. Secondary end points included OS and objective response. Patients who had received previous adjuvant or neoadjuvant therapies containing a PD-1, CTLA-4, BRAF, or MEK inhibitor (or a combination of BRAF and MEK inhibitors) were eligible if the therapy was completed at least 6 months before the date of recurrence. Key exclusion criteria were uveal melanoma and active, untreated brain or leptomeningeal metastases.[16]

Grade 3 or 4 treatment-related adverse events occurred in 18.9% of the patients in the relatlimab-nivolumab group and 9.7% of patients in the nivolumab-alone group. Treatment-related adverse events led to treatment discontinuation in 14.6% of patients in the relatlimab-nivolumab group and 6.7% of patients in the nivolumab-alone group. The most common categories of immune-mediated adverse events that occurred in the relatlimab-nivolumab group were hypothyroidism or thyroiditis (18.0%), rash (9.3%), and diarrhea or colitis (6.8%). Myocarditis occurred in 1.7% of the patients in the relatlimab-nivolumab group and 0.6% of patients in the nivolumab-alone group.

A multinational, phase II/III, double-blind trial (RELATIVITY-047 [NCT03470922]) included 714 patients with previously untreated, histologically confirmed, unresectable stage III or IV melanoma. Patients were randomly assigned in a 1:1 ratio to receive either 160 mg of relatlimab and 480 mg of nivolumab in a fixed-dose combination (n = 355) or 480 mg of nivolumab (n = 359). The characteristics of the patients at baseline were well balanced between the treatment groups. Both therapies were given in a single 60-minute IV infusion every 4 weeks. The primary end point was PFS assessed according to RECIST, version 1.1. Secondary end points included OS and objective response. Patients who had received previous adjuvant or neoadjuvant therapies containing a PD-1, CTLA-4, BRAF, or MEK inhibitor (or a combination of BRAF and MEK inhibitors) were eligible if the therapy was completed at least 6 months before the date of recurrence. Key exclusion criteria were uveal melanoma and active, untreated brain or leptomeningeal metastases.[16]

The relatlimab-nivolumab combination was beneficial compared with nivolumab alone, regardless of LAG-3 expression or BRAF pathogenic variant status. OS and response rate data have not been reported.