Aims: NIVO+IPI and NIVO have superior clinical activity vs IPI in MEL patients, irrespective of PD-L1 tumor expression. We describe PD-L1 as a biomarker for NIVO+IPI and NIVO efficacy across phase 2 (CheckMate 069) and phase 3 (CheckMate 066/067) trials.
Methods: Patients (N=832) received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4 or NIVO 3 mg/kg Q2W, followed by NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. Tumor tissue was assessed for PD-L1 expression using Dako immunohistochemistry. Minimum follow-up was 18 months.
Results: Among patients with PD-L1 expression ≥5%, median progression-free survival (mPFS) of NIVO+IPI was not reached (NR) and was 22.0 months for NIVO alone (hazard ratio [HR]: 0.99, 95% CI: 0.66-1.46). For patients with low to no PD-L1 (<5%), mPFS was 11.1 months for NIVO+IPI and 4.9 months for NIVO (HR: 0.70, 95% CI: 0.57-0.87). Objective response rate (ORR) was higher with NIVO+IPI vs NIVO in patients with ≥5% (68.5% vs 59.0%) and <5% (54.9% vs 39.7%) PD-L1 expression. Median duration of response was NR in both PD-L1 subgroups for NIVO+IPI, and 20.8 and 22.3 months in NIVO ≥5% and <5% PD-L1 subgroups, respectively. Treatment-related grade 3/4 adverse events were consistent with earlier reports (NIVO+IPI: 56.5%, NIVO: 18.2%) and did not differ by PD-L1 expression.
Conclusions: While patients with ≥5% PD-L1 tumor expression have better efficacy outcomes, those with <5% PD-L1 expression still benefit from NIVO+IPI or NIVO. Among patients with high PD-L1 expression, mPFS of NIVO+IPI and NIVO was similar, but the ORR of NIVO+IPI was numerically higher across PD-L1 subgroups. As survival data have not yet matured, caution is advised when applying these results to assess the relative benefit of NIVO+IPI vs NIVO.