Aims: NIVO and IPI combination therapy showed a significant improvement in objective response rate and progression-free survival (PFS) vs IPI alone in phase 2 and 3 studies in MEL patients. We report the first OS results evaluating NIVO+IPI in a randomized, controlled trial.
Methods: In this phase 2 trial (CheckMate 069), 142 patients were randomly assigned 2:1 (stratified by BRAF mutation status) to receive NIVO 1 mg/kg + IPI 3 mg/kg or IPI 3 mg/kg + placebo Q3W x 4, followed by NIVO 3 mg/kg or placebo, respectively, Q2W until progression or unacceptable toxicity. Primary endpoint was objective response rate among patients with BRAF wild-type MEL. Secondary endpoints included PFS in patients with BRAF wild-type tumors and safety. OS was an exploratory endpoint. Minimum follow-up was 2 years (database lock: February 2016).
Results:We randomized 95 patients to NIVO+IPI and 47 to IPI (72 and 37 patients with BRAF V600 wild-type tumors, respectively). OS rate in patients with BRAF wild-type tumors was 69% for NIVO+IPI vs 53% for IPI alone; median OS had not been reached in the NIVO+IPI group and was 24.8 months for the IPI group (hazard ratio 0.58, 95% CI 0.31-1.08). Two-year PFS rates were 54% for NIVO+IPI vs 11% for IPI alone; median PFS had not been reached in the NIVO+IPI group and was 4.4 months for the IPI group (hazard ratio 0.35, 95% CI 0.21-0.59, p<0.0001). Grade 3-4 treatment-related adverse events (AEs) were reported more frequently in NIVO+IPI patients (54%) vs IPI alone (20%) and led to discontinuation in 30% vs 9%, respectively.
Conclusions: The combination of first-line NIVO+IPI led to a numerically higher 2-year OS rate than first-line IPI alone in patients with MEL. There were no new safety signals with longer follow-up.