PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.
Publication/Presentation Date
12-30-2024
Abstract
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.
Volume
15
Issue
1
First Page
10743
Last Page
10743
ISSN
2041-1723
Published In/Presented At
Stein, M. N., Dumbrava, E. E., Teply, B. A., Gergis, U. S., Guiterrez, M. E., Reshef, R., Subudhi, S. K., Jacquemont, C. F., Senesac, J. H., Bayle, J. H., Scripture, C. D., Chatwal, M. S., Bilen, M. A., Stadler, W. M., & Becerra, C. R. (2024). PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial. Nature communications, 15(1), 10743. https://doi.org/10.1038/s41467-024-53220-6
Disciplines
Medicine and Health Sciences
PubMedID
39737899
Department(s)
Department of Medicine
Document Type
Article
