Jessica Hassel, MD, University Hospital Heidelberg, Germany, discusses the phase 3 trial evaluating the combination of the IO102-IO103 cancer vaccine and pembrolizumab in the first-line setting for the treatment of patients with advanced melanoma. While the significance threshold was “narrowly missed,” there was a benefit seen with the combination across all subgroups when compared to pembrolizumab alone. 

Dr Hassel concluded, “This trial demonstrates that there is an efficacy of immune-modulatory vaccines in patients with metastatic melanoma in the first line.”

These data were first presented at the 2025 European Society for Clinical Oncology (ESMO) Annual Congress in Berlin, Germany.

Transcript:

Dear colleagues, my name is Jessica Hassel, I'm a dermato-oncologist and I'm the head of the section of Dermato-Oncology at the University Hospital in Heidelberg, Germany. And at this year's ESMO, I presented the results on a randomized phase 3 study using the cancer vaccine IO102-103 in combination with pembrolizumab versus pembrolizumab alone. 

What is IO102-103? This is an immune-modulatory, off-the-shelf cancer vaccine and it consists of 2 peptides from IDO1 and PD-L1. It's administered subcutaneously and then taken up by antigen-presenting cells, thereby leading to an activation and expansion of specific T-cells against IDO and PD-L1. IDO and PD-L1 is expressed in the tumor microenvironment and thereby the vaccine leads to an elimination of, on one hand, tumor cells and, on the other hand, mainly immunosuppressive cells such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. 

In this phase 3 study, more than 400 patients were randomized 1-to-1 to receive either the combination of this cancer vaccine plus pembrolizumab versus pembrolizumab alone, every 3 weeks up to 2 years. The primary endpoint was progression-free survival. The Kaplan-Meier curves on progression-free survival show a separation of the curve, with a median progression-free survival of 19.4 months for the combination and 11 months for pembrolizumab. The hazard ratio was 0.77, however the significance threshold was narrowly missed with a P-value of 0.4056. Nevertheless, you see across all subgroups a benefit for the combination compared to pembrolizumab alone, and especially in patients with BRAF-mutated tumors or PD-L1–negative tumors, and in patients with an elevated LDH.

Concerning tolerability, it's important to say that this vaccine didn't add any systemic toxicity to the known safety profile of pembrolizumab. The only event that was recognized in half of the patients were mild injection site reactions such as erythema, swelling, and granulomas. There was only one grade 3 injection site reaction noted. 

First translational investigations demonstrate that patients showing a high vaccination-specific response against both peptides had the best progression-free survival, compared to patients who had a high response only against 1 of the peptides. And the worst progression-free survival was seen in patients with no or low responses. 

Taken together, I think this trial demonstrates that there is an efficacy of immune modulatory vaccines in patients with metastatic melanoma in the first line. However, the significance threshold was narrowly missed in this study. And with this, I'd like to thank you for your attention.

Source:

Hassel J. IO102-IO103 cancer vaccine plus pembrolizumab for first-line (1L) advanced melanoma: Primary Phase 3 results (IOB-013/KN-D18). Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. Abstract LBA 53.