Correlation of serum cytokines with clinical responses in patients treated with BPX-101, a drug-activated vaccine for metastatic castration-resistant prostate cancer (mCRPC).

Abstract

167 Background: We report the correlation of clinical and immune monitoring results for subjects enrolled in a phase I/IIa clinical trial of BPX-101, a drug-activated dendritic cell vaccine for mCRPC. Methods: Men with progressive mCRPC were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and activating agent AP1903. BPX-101 was administered intradermally every 2 weeks for 6 doses, during the induction phase, and for non-progressing 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. Blood samples for immune monitoring were collected weekly during the induction phase, and before and one week after each maintenance dose. GM-CSF, TNF-α, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, and RANTES levels were measured by Luminex microspheres, and IL-6 by ELISA. Results: Planned enrollment of 12 subjects is complete, including 3 each at 4 × 106 and 12.5 × 106 cells/dose, and 6 at 25 x 106 cells/dose. A pattern of spiking levels of serum cytokines one week after each dose, returning to baseline the following week, was observed in subjects with greater disease burden. In one low dose subject who experienced a PR after one year on study, panel cytokines spiked 4-fold on average after each induction phase dose, less than 2-fold after the first two boosters, and between 6-fold and 56-fold after the final three boosters. IL-6, which had declined during the induction phase to below 1 pg/mL through two boosters, spiked between 1,680-fold and 13,000-fold after each of the last three boosters. In a second, high dose subject (#1008), who experienced a near CR of multiple lung metastases with otherwise stable disease, panel cytokines spiked 150-fold on average during the induction phase. In both cases, TNF-α, MIP-1α and MIP-1β spiked the most, including a more than 1,000-fold average spike in TNF-α for subject 1008. Cytokine spikes were not associated with AEs. Conclusions: BPX-101 induces a spiking pattern of cytokine elevations after each dose. In patients who experienced measurable disease reductions, more dramatic spikes in serum inflammatory cytokine levels were seen. [Table: see text]