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).
ABSTRACT
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 ≤1 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 (induction phase), and for non-progressing patients, every 8 weeks for up to 5 doses (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 receiving 4, 12.5 or 25 x 106 cells/dose has been completed. Median Halabi-predicted survival was 13.8 months, and 9/12 subjects had Gleason scores ≥8. Toxicities were generally mild and expected (e.g. injection site reactions), with no DLTs. One high dose subject experienced a single acute grade 2 cytokine reaction during infusion of AP1903 at the second vaccination, but continued induction without further drug-related adverse events. Two subjects went off protocol prior to the end of induction due to progression, and the remaining 10/12 achieved a best response of stable disease or better. Significant PSA responses were seen in two subjects (313 ng/mL to 170 ng/mL [46% decline], and 1070 ng/mL to 169 ng/mL [85% decline]). One post-docetaxel low dose subject achieved a RECIST PR, and one chemo-naive mid dose subject with extensive visceral, nodal, and bone metastases experienced a RECIST CR with docetaxel-based chemotherapy after induction and maintains an undetectable PSA (0.025 ng/mL) 14 months after enrollment. A third, high dose subject experienced near complete elimination of multiple lung metastases with otherwise stable disease by the end of induction.
Conclusions: BPX-101 can be reliably manufactured and safely administered, followed by AP1903, at doses of at least 25 x 106 cells. Contrary to the growing consensus that cancer vaccine therapy improves survival without short-term response, BPX-101-treated patients have experienced measurable disease responses, including elimination of poor-risk visceral disease.