A Phase II Trial Combining Personalized Neoantigen Peptide Vaccines with Precision Radiotherapy for Advanced Cancers

This is an open-label, multicenter Phase II randomized trial. Patients with advanced solid tumors (including melanoma, glioblastoma, lung cancer, and colorectal cancer) who have failed first-line therapy are randomized 1:1 to receive either personalized neoantigen peptide vaccine plus conventional treatment (with high and low dose radiotherapy) or placebo plus conventional treatment. A one-way crossover lets placebo patients switch to the vaccine arm if their disease progresses. Patients must have at least one predicted high-quality tumor neoantigen, an ECOG score of 0-2, and projected survival of at least 3 months.

Neoantigen vaccines are one of the most personalized cancer treatments possible — they're designed from each patient's own tumor mutations. But in advanced cancers, they haven't worked well alone because the immune system is too suppressed and tumor burden too high. This trial tests a promising solution: using targeted radiation to prime the immune system before vaccination, potentially making the vaccine far more effective in patients with few options left.

Personalized cancer vaccines have generated excitement but have hit a wall in late-stage disease. This trial represents the broader push to combine immunotherapy with other modalities — in this case, using radiation not just to kill tumors but to make them more visible to the immune system. The basket-trial design across multiple cancer types also reflects a shift toward mutation-based rather than organ-based cancer treatment, which could make personalized vaccines more practical and affordable at scale.

No results are available yet — this is a protocol description only. The open-label design means patients and doctors know who is receiving the vaccine, which could influence assessments. Manufacturing personalized vaccines requires tumor sequencing and neoantigen prediction, which may not be accessible outside major medical centers. The crossover design, while ethical, may complicate interpretation of overall survival data.