Multinational phase 3 trial of IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in untreated advanced melanoma

The investigational, immune-modulatory cancer vaccine IO102-!O103 targets both tumor cells and immune-suppressive cells within the tumor microenvironment through activation and expansion of T cells agains indoleamine 2,3-dioxygenase 1-positive and/or PD-L1-positive cells. The multinational phase 3 IOB-013 trial evaluated the vaccine in 407 patients with untreated advanced melanoma. Patients were randomized 1:1 to subcutaneous IO102-IO-103 85 μg plus intravenous pembrolizumab 200 mg every 3 weeks or pembrolizumab alone for up to 2 years. The primary endpoint was progression-free survival (PFS) by blinded independent central review. The median PFS was 19.4 months with the combination versus 11.0 with pembrolizumab alone (HR 0.77; p=0.0558). A longer PFS was observed in the combination arm across most subgroups, notably in patients with PD-L1-negative tumors, anti-PD-1 naïve patients, proto-oncogene BRAF mutated tumors, or elevated lactate dehydrogenase. There was no increase in the frequency of grade ≥3 treatment-related adverse events or of serious adverse events in the vaccine group. Local injectio site reaction (56% of patients) were mostly grade 1 or 2. The authors conclude that addition of IO102-IO103 to first-line pembrolizumab was associated with prolonged PFS in patients with advanced melanoma; hwever, statistical significance was missed for the primary endpoint.