Results of a phase I/II clinical trial of BPX-101, a novel drug-activated dendritic cell (DC) vaccine for metastatic castration-resistant prostate cancer (mCRPC).

132 Background: We report results of a phase I/II clinical trial of BPX-101, a drug- activated autologous DC vaccine targeting PSMA. METHODS Men with progressive mCRPC following up to one prior chemotherapy regimen were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and CD40 activating agent AP1903. BPX-101 was administered intradermally every 2 weeks for 6 doses, during the induction phase, and for nonprogressing patients, every 8 weeks for up to 5 doses during the maintenance phase. AP1903 (0.4 mg/kg) was infused 24 hours after each BPX-101 dose. Radiologic evaluation was performed every 12 weeks. RESULTS Planned enrollment of 12 subjects has been completed, including 3 each at 4 × 106 and 12.5 × 106 cells/dose, and 6 at 25 × 106 cells/dose. All vaccine products were releasable. Median Halabi- predicted survival was 13.8 months. Two subjects went off protocol prior to the end of induction due to progression, 8 reached end of induction, and 2 are nearing completion of induction. Toxicities (e.g. injection site reactions) were generally mild. One high dose subject experienced a single acute cytokine reaction during infusion of AP1903 at the second vaccination, but continued induction without further drug-related adverse events. Notably, one post- docetaxel subject in the low dose cohort achieved a RECIST PR, and one chemo-naive subject in the mid-dose cohort with extensive visceral, nodal, and bone metastases experienced a RECIST CR with docetaxel-based chemotherapy after induction and maintains an undetectable ultrasensitive PSA (0.009 ng/mL) 10 months after enrollment. A third subject, in the high-dose cohort, experienced near complete elimination of multiple lung metastases with otherwise stable disease by the end of induction. Robust immune responses were seen in all three. CONCLUSIONS BPX-101 can be reliably manufactured and safely administered, followed by AP1903, at doses of at least 25 × 106 cells. Contrary to the observation that cancer vaccine therapy improves survival without short-term response, BPX-101-treated patients have experienced measurable disease responses, including near elimination of poor-risk visceral disease. [Table: see text].