Immune-Modulatory and mRNA-Based Cancer Vaccines Could Boost Benefit With ICIs Across Solid Tumors

Continued interest in the development of novel cancer vaccines represents a desire to extend the benefits seen with immunotherapy in select cancers to broader patient populations. In the video above, the following experts review new data presented during the 2025 ESMO Congress that confirm the promise of therapeutic cancer vaccines across solid tumors:

Jessica Hassel, MD, a dermato-oncologist working at the University Hospital in Heidelberg, Germany.

Adam Grippen, MD, PhD, a resident in radiation oncology and fellow in the T32 Cancer Nanotechnology Fellowship at the University of Texas MD Anderson Cancer Center in Houston.

Jonathan W Riess, MD, MS, director of Thoracic Oncology and associate professor of medicine in the Division of Hematology and Oncology at the University of California, Davis Comprehensive Cancer Center.

Highlighted studies included the phase 3 IOB-013 (NCT05155254) study evaluating the investigational immune-modulatory therapeutic cancer vaccine IO102-IO103 in melanoma; a phase 2 basket trial (NCT05077709) evaluating first-line IO102-IO103 plus pembrolizumab (Keytruda) in patients with head and neck squamous cell carcinoma and advanced non–small cell lung cancer; and a retrospective analysis of mRNA-based COVID vaccines administered after immune checkpoint inhibition in patients with cancer.

Watch the video or read the transcript below to learn more!

[Transcript]

LBA53 - IO102-IO103 cancer vaccine plus pembrolizumab for first-line (1L) advanced melanoma: Primary phase III results (IOB-013/KN-D18)

Hassel: In cutaneous melanoma, we already have quite good immunotherapies. We have the immune checkpoint blockade, either with PD-1 monotherapy or the double checkpoint blockade together with a CTLA-4 antibody. Nevertheless, you have resistance to anti-PD-1. The aim was actually to get new tumor-specific responses, because immune checkpoint blockers only work in patients who already have an immune response, and then you can activate this immune response. But with a vaccine, you want to create new immune responses to lift the level a bit higher in cutaneous melanoma; that actually was the aim.

What this trial clearly shows is that cancer vaccines can be effective in metastatic cancer—I would not say only in melanoma. The special thing about this vaccine is that it changes the tumor microenvironment. It is not really aiming for the tumor cells, but for immunosuppressive cells. This is something very new, and it shows that that might be a very good effort.

1557P - IO102-IO103 cancer vaccine plus pembrolizumab for first-line (1L) treatment of advanced solid tumors: Final results of a phase II basket trial

Riess (1.03-2.21; 3.58-4.15): In terms of this basket trial, participants included advanced metastatic non-small cell lung cancer and advanced metastatic head and neck squamous cell carcinoma. They had to be PD-L1 high, where the standard of care, or a standard of care, is single-agent pembrolizumab. AThe idea was to use this immunomodulatory peptide against IDO1 and PD-L1 to make the tumors "hotter" and to see if we could observe a signal of more activity in head and neck squamous cell cancer and non-small cell lung cancer.

What we showed was that [the IO102-IO103 vaccine] was safe and tolerable. The efficacy primary endpoint, overall response rate, was met for head and neck squamous cell cancer, and that also showed favorable activity in non-small cell lung cancer.

I think [this trial] addresses an unmet need. Even in PD-L1–high HNSCC and non–small cell lung cancer, there are patients that respond suboptimally or have a shorter duration of response, even though that's kind of the target population for PD-1 efficacy. There still is room for improvement.

LBA54: mRNA-based COVID vaccines prompt improved responses to immunotherapy

Grippen (3.57-4.59): All of [these data] are retrospective, and so we cannot implement these findings in the clinic yet. But the data are exciting, and it really deserves to be validated in a phase 3 clinical trial. Our hope is that if we can demonstrate that these vaccines improve responses to immune checkpoint blockade, because they are so widely available, they could quickly be integrated into the clinical care regimen for a large number of patients. The other exciting component of this is that the COVID mRNA vaccines were not designed for this purpose, and we are showing this effect even with a vaccine that is not designed specifically for this. It suggests that we may be able to develop even more effective, universal RNA therapeutics that would improve responses to immune checkpoint blockade in patients with immunologically cold tumors.