Overall survival (OS) analysis of a phase l trial of a vector-based vaccine (PSA-TRICOM) and ipilimumab (Ipi) in the treatment of metastatic castration-resistant prostate cancer (mCRPC).

Abstract

2550 Background: Therapeutic cancer vaccines have demonstrated great promise in the treatment of mCRPC. PSA-TRICOM is a vector-based vaccine that targets PSA and includes the transgenes for 3 human costimulatory molecules (ICAM-I, LFA-3, and B7.1) to enhance T-cell activation. A multicenter, randomized phase II trial demonstrated a significant OS advantage versus placebo in mCRPC. A smaller NCI phase II study demonstrated an association of OS with PSA-specific immune response (IR). CTLA-4 is a molecule expressed by activated T-cells and signaling through this turns off the IR. Preclinical models demonstrate that a blockade of CTLA-4 can enhance T-cell mediated IR to vaccine. Ipi is a monoclonal antibody that blocks the moderating effects CTLA-4. Methods: Patients (pts) with mCRPC were treated in this phase I, dose- escalation study. All pts received PSA-TRICOM on days 1, 15, 29 and then monthly. Ipi was administered at 1, 3, 5, or 10 mg/kg in sequential dose levels (DL) monthly. After 6 months (mos), pts could receive maintenance Ipi every 3 mos. Predicted OS was determined for each pt. Although the first 6 pts enrolled received prior chemotherapy, the remainder of pts enrolled were chemotherapy naive (CN). Results: The study has fully accrued 30 pts. Median on-study age was 69 years (range: 49–81); median PSA was 49 mcg/L (3–729), median Gleason score was 8 (4-10), and median PSA doubling time was 2.3 mos. The median time to radiographic progression for CN pts was 5.9 mos. The median Halabi predicted OS for all pts was 18.5 mos. The median OS for all pts was 31.8 mos with a 74% survival probability at 24 mos. The median OS for CN pts is 30.9 months. There was no significant difference in OS based on DL. 4 of 6 evaluable pts at the higher DLs had a greater than 2-fold increase in antigen-specific T-cell responses. Conclusions: Two phase II trials in CN mCRPC treated 114 pts with this same vaccine demonstrating an OS of ∼26 mos. These data suggest that the addition of immune checkpoint inhibition may augment the clinical benefit of vaccines. Additional, randomized trials are required to further investigate immune checkpoint inhibition and vaccine in mCRPC. No significant financial relationships to disclose.