Phase II trial of anti-idiotypic p53 peptides (Pentrys) plus granulocyte-macrophage colony-stimulating factor in patients with hormone-refractory prostate cancer

Background: p53 overexpression occurs commonly in hormone-refractory prostate cancer (HRPC). T-cell responses against p53 could potentially mediate an antitumor effect. We investigated a novel system of vaccination using three peptides derived from a mouse-antihuman p53 antibody (Pentrys) in men with HRPC. Patients and methods: A phase II, single-arm, open-label study of Pentrys peptides admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF) was injected intradermally in men with HRPC, rising prostate-specific antigen (PSA) and minimal symptoms. The primary objective was to determine clinical responses as measured by PSA. Secondary objectives were to determine duration of PSA response, progression-free survival (PFS), anti-p53 antibody response, and safety. Patients received study drug on weeks 1, 3, 5, 9, 13 and 17. Patients suitable for ongoing treatment received two more doses at weeks 21 and 25. Tumor status was assessed at baseline, week 17 and 3 months after the final injection. Results: Forty patients entered the study and were evaluable for safety; 39 were evaluable for efficacy. Thirty patients completed at least 16 weeks of treatment. One PSA response was observed that lasted 85 days. Median PFS was 56 days. Treatment was generally well tolerated. Only one dose-limiting toxicity was observed (allergic rhinitis and urticaria). Five patients had anti-p53 antibodies at screening. Two patients developed anti-p53 antibodies during the study, including the patient with the PSA response. Conclusions: Pentrys administered with GM-CSF by intradermal injection is well tolerated. Only one PSA response was seen and anti-p53 seroconversion was observed in two patients. Pentrys has minimal clinical activity in this patient population.