An investigational, immune-modulatory cancer vaccine, IO102-IO103, when combined with pembrolizumab results in sustained progression-free survival (PFS) compared with pembrolizumab alone in patients with advanced melanoma, reports a study.
“Patients treated with IO102-IO103 plus pembrolizumab demonstrated a numerically longer median PFS of 19.4 months compared with 11.0 months for patients treated with pembrolizumab alone; however, statistical significance was not met on the primary endpoint,” the researchers said.
Four hundred seven patients with untreated advanced melanoma were included in this open-label phase III trial. Participants were randomized in a 1:1 ratio to receive either subcutaneous IO102-IO103 (85 μg each) plus pembrolizumab 200 mg intravenously every 3 weeks or pembrolizumab alone for up to 2 years. PFS by blinded independent central review per RECIST v1.1 was the primary endpoint.
PFS benefit
IO102-IO103 plus pembrolizumab yielded a longer median PFS than pembrolizumab alone (19.4 months, 95 percent confidence interval [CI], 9.7 to not reached vs 11.0 months, 95 percent CI, 6.0‒14.8; hazard ratio [HR], 0.77, 95 percent CI, 0.58‒1.00; p=0.0558), but the threshold for statistical significance (p≤0.045) was not met. [Ann Oncol 2026;37:999-1010]
Across most subgroups, the combination therapy demonstrated a longer PFS, particularly in patients with PD-L1-negative tumours (median PFS 16.6 vs 3.0 months; HR, 0.54, 95 percent CI, 0.35‒0.85), anti-PD-1 naïve patients (24.8 vs 11.0 months; HR, 0.74, 95 percent CI, 0.56‒0.98), proto-oncogen B-Raf-mutated tumours, or elevated lactate dehydrogenase.
Furthermore, no increase was observed in the frequency of treatment-related adverse events (AEs) grade ≥3 (14.5 percent vs 15.6 percent) or serious AEs (32.0 percent vs 32.3 percent) in the vaccine arm. More than half of the vaccinated patients (56.0 percent) reported local injection site reactions, which were mostly grade 1 or 2 in severity.
Antitumour activity
“These data support the potential benefit of an immune-modulating cancer vaccine in combination with pembrolizumab in patients with advanced melanoma,” the researchers said.
Preclinical and translational studies previously showed the mechanistic immune modulation by IO102-IO103 and corresponding antitumour activity. The vaccine’s antitumour activity in an anti-PD-1 resistant B16F10 melanoma model correlated with reductions in immunosuppressive myeloid cells and increase in the infiltration of effector T cells. [Cancer Immunol Res 2022;10:571-580]
Furthermore, in vitro studies exhibited how the immune response generated by IO102-IO10 against IDO1+ target cells converts the neighboring PD-L1-negative cells into PD-L1 positive. [Cancer Res 2024;84(suppl 6):4094]
High expectations
The current study was designed to prove an assumed effect (HR) size of 0.65, with 91-percent power based on assumptions from a phase I/II trial, according to the researchers.
“Sample size is linked to trial assumptions including those about treatment effect size, which were based on high expectations from a small study, highlighting the challenges of translating efficacy into a larger trial population,” the researchers said.
“Therefore, the main reasons that the primary endpoint was not met in this study are that it was based on assumptions that were too ambitious for the expected improvement of the clinical outcome compared with anti-PD-1 monotherapy and that the effect was smaller in patients with PD-L1-positive tumours,” they added.
The investigational vaccine IO102-IO103 works by targeting both tumour cells and immune-suppressive cells within the tumour microenvironment through “activation and expansion of T cells against indoleamine 2,3-dioxygenase 1–positive and/or PD-L1-positive cells,” the researchers said.