靶向 PSCA 的 BPX-601 CAR-T 细胞经 rimiducid 药理激活治疗转移性胰腺癌和前列腺癌：一项 I 期剂量递增试验

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid. Thirty-three patients received BPX-601 with or without rimiducid, 24 patients with mPDAC and 9 with mCRPC.

Two dose-limiting toxicities and two treatment-related deaths occurred in the highest-dose mCRPC cohort, after which the study was terminated, without determination of the RP2D. Two mCRPC patients experienced partial responses (one unconfirmed), and 56% of mCRPC patients achieved 50% reduction in prostate-specific antigen. BPX-601 cell expansion, long-term persistence in peripheral blood, and tumor infiltration were observed.

Rimiducid increased circulating inflammatory cytokines/chemokines consistent with GoCAR-T cell activation. These results suggest that pharmacological activation of GoCAR-T cells is feasible and may offer a promising avenue to control chimeric antigen receptor-T cell activity with continued dose-optimization to improve tolerability.