New Randomized Phase 2 Trial Tests Vaccine Plus PSMA×CD3 Immunotherapy in Biochemical Recurrence

A new randomized phase 2 trial will test an immunotherapy strategy specifically in men with biochemical recurrence of prostate cancer after local treatment with curative intent, meaning patients whose PSA is rising again after surgery and/or radiotherapy but who are not yet receiving further systemic treatment.
The study plans to enrol up to 84 patients and randomize them 1:1:1 to three groups: the prostate cancer multi-peptide vaccine VAC-XS15-PC01, the PSMA×CD3 bispecific antibody CC-1, or the combination of both. No other anticancer therapy is planned during trial participation.
CC-1 binds PSMA on prostate cancer cells and CD3 on T cells, physically redirecting T cells towards the tumour. It was developed in a format intended to prolong half-life while reducing unwanted systemic T-cell activation. PSMA expression on tumour-associated vessels may also provide an additional anticancer mechanism.
The vaccine takes a different approach. VAC-XS15-PC01 contains 10 HLA-restricted prostate cancer-associated peptides, selected through immunopeptidomic analyses, combined with the TLR1/2 agonist XS15 and Montanide. Its goal is to expand T cells that specifically recognize prostate cancer antigens.
The most interesting feature of the study is its three-arm randomized design. Instead of simply assuming that vaccination and a bispecific antibody should work better together, the trial can directly compare vaccine alone, CC-1 alone and their combination. This should help determine whether vaccine priming genuinely strengthens PSMA-directed T-cell engagement.
The biochemical-recurrence setting is also important. Tumour burden is generally much lower than in metastatic castration-resistant disease, potentially giving immunotherapy a better chance before extensive tumour-mediated immune suppression develops.
The trial will closely track PSA and immune responses. A key efficacy measure is PSA50, a decline of at least 50% from baseline, alongside detailed analyses of CC-1-induced immune activity and vaccine immunogenicity.

What makes this trial particularly interesting is that it tests a clear biological hypothesis: can a prostate cancer vaccine generate more tumour-specific T cells, while a PSMA×CD3 bispecific antibody then redirects and amplifies their activity against cancer cells? If the combination clearly outperforms both monotherapies, it could provide an important proof of concept for combining vaccination with bispecific T-cell engagement in early recurrent prostate cancer.

Clinical trial.