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.
Nature communications. 2024 Dec 30*** epublish ***
Mark N Stein, Ecaterina E Dumbrava, Benjamin A Teply, Usama S Gergis, Martin E Guiterrez, Ran Reshef, Sumit K Subudhi, Céline F Jacquemont, Joseph H Senesac, J Henri Bayle, Charity D Scripture, Monica S Chatwal, Mehmet A Bilen, Walter M Stadler, Carlos R Becerra
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA., The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ., University of Nebraska Medical Center, Omaha, NE, USA., Thomas Jefferson University, Philadelphia, PA, USA., Hackensack University Medical Center, Hackensack, NJ, USA., The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bellicum Pharmaceuticals, Inc., Houston, TX, USA., H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA., University of Chicago, Chicago, IL, USA., Baylor University Medical Center, Dallas, TX, USA.