IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in melanoma
In brief
Melanoma vaccine combo added 8 months of median progression-free survival, but missed significance
In 407 patients with untreated advanced melanoma, adding IO102-IO103 to pembrolizumab increased median progression-free survival from 11.0 to 19.4 months, but the trial missed its prespecified threshold for statistical significance. Severe and serious adverse events were no more frequent with the vaccine, though injection-site reactions were common; whether the apparent benefit is real needs confirmation.
- Journal
- Annals of Oncology (Q1)
- Published
- 1 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- J C Hassel, A Arance, M S Carlino, L Mortier, P A Ascierto, P Rutkowski, et al.
- PMID
- 42025759
- DOI
- 10.1016/j.annonc.2026.04.010
Why clinicians should know about it
- Picked for Dermatology (top studies of the week, 25 October 2026): Phase III trial of IO102‑IO103 vaccine plus pembrolizumab in melanoma
Abstract
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-positive and/or programmed death ligand 1 (PD-L1)-positive cells. PATIENTS AND METHODS: This open-label, phase III trial randomly assigned 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 6.0-14.8) for pembrolizumab [hazard ratio (HR) (95% CI) 0.77 (0.58-1.00), 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 0.35-0.85)], anti-PD-1 naïve patients [24.8 versus 11.0 months (HR 0.74, 95% CI 0.56-0.98)], 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 PFS 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.