214 Background: A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase 2 trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances anti-tumor effects in patients with castration-resistant prostate cancer (CRPC). Methods: In this double-blind, placebo-controlled, randomized, phase 2 study, we enrolled chemotherapy-naïve patients with progressive CRPC from 10 medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to either KRM-20 combined with docetaxel and dexamethasone or placebo with docetaxel and dexamethasone. Patients initially received 5 weekly subcutaneous KRM-20 (20 mg) or placebo injections with daily oral dexamethasone (1 mg) following 5 courses of docetaxel (70 mg/m2 every 3 weeks). The primary endpoint was to compare each treatment for prostate-specific antigen (PSA) decline. Results: Between Jul 31, 2013 and Jul 11, 2014, 51 patients were enrolled to the trial: 25 were assigned to the KRM-20 arm, and 26 were allocated to the placebo arm. Mean % PSA levels from baseline in the KRM-20 arm significantly decreased during the treatment compared witht those in the placebo arm ( P = 0.028, MANOVA). Human leukocyte antigen matched peptide-specific immunoglobulin G ( P = 0.018) and CTL ( P = 0.007) responses in the KRM-20 arm significantly increased after the treatment. The appearance of myeloid-derived suppressor cells in the KRM-20 arm significantly decreased after the treatment ( P = 0.007). The addition of KRM-20 did not result in increased toxicity. There was no between-group differences in progression-free or overall survival. Conclusions: These findings suggest potential clinical benefits for the combined use of KRM-20 with docetaxel and dexamethasone in patients with CRPC. Clinical trial information: UMIN000011028.
Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial
