IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in melanoma

BACKGROUND: IO102-IO103, an investigational, immune-modulatory cancer vaccine, targets both tumor cells and immune-suppressive cells within the tumor microenvironment through activation and expansion of T cells against indoleamine 2,3-dioxygenase 1(IDO1)-positive and/or programmed death ligand 1 (PD-L1)-positive cells. PATIENTS AND METHODS: This open-label, Phase 3 trial randomized 407 patients with untreated advanced melanoma in a 1:1 ratio to receive subcutaneous IO102-IO103 (85 μg each) plus pembrolizumab 200 mg intravenously every 3 weeks or pembrolizumab alone for up to 2 years. The primary endpoint was progression-free survival (PFS) by blinded independent central review per RECIST v1.1. RESULTS: The median PFS was 19.4 months (95% confidence interval CI, 9.7 to not reached) for IO102-IO103 plus pembrolizumab versus 11.0 months (95% CI, 6.0 to 14.8) for pembrolizumab (hazard ratio HR 95% CI, 0.77 0.58 to 1.00; P = 0.0558); the statistical significance threshold (P ≤ 0.045) was missed. A longer PFS was observed in the combination arm across most subgroups, notably in patients with PD-L1-negative tumors (median PFS 16.6 versus 3.0 months HR, 0.54; 95% CI, 0.35 to 0.85), anti-PD-1 naïve patients (24.8 versus 11.0 months HR, 0.74; 95% CI, 0.56 to 0.98), proto-oncogene B-Raf (BRAF) mutated tumors, or elevated lactate dehydrogenase. There was no increase in the frequency of treatment-related adverse events grade ≥3 (14.5% versus 15.6%) or of serious adverse events (32.0% versus 32.3%) in the vaccine arm. Local vaccine-related injection site reactions were reported in 56.0% of patients and were mostly grade 1/2. CONCLUSIONS: IO102-IO103 plus pembrolizumab prolonged progression-free survival compared with pembrolizumab alone in patients with advanced melanoma in the first-line setting; however, statistical significance was missed for the primary endpoint. The combination was well tolerated with no added significant systemic toxicity. These data show the potential benefit of this combination in untreated advanced melanoma.