Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Clinical Trial
Official title:
Phase I, Open-Label Study of Dually Armored Chimeric Antigen Receptor (CAR) T Cells (TmPSMA-02) in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
This is a Phase I, open-label dose finding study to assess the safety, tolerability, manufacturing feasibility, and preliminary efficacy of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer (mCRPC). Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.
This is a Phase I, open-label dose finding study to assess the safety, tolerability, manufacturing feasibility, and preliminary efficacy of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer (mCRPC). Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design as described below. Dose escalation will begin with Dose Level 1 as follows: - Dose Level 1 (N = 3 to 6): Subjects will receive a single dose of 5 x 107 TmPSMA-02 CAR T cells via IV infusion administration on Day 0, following lymphodepletion with fludarabine and cyclophosphamide. This dose level will be evaluated as follows: - If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. - If 0 DLT/3 subjects or 1 DLT/6 subjects occur, the study will advance to Dose Level 2 (DL2). - In the event that 2 or more DLTs occur at Dose Level 1 (DL1), enrollment at this dose level will be stopped and Dose Level -1 (DL-1) will be opened. In Dose Level -1, subjects will receive a de-escalated dose of 1 x 107 TmPSMA-02 CAR T cells following lymphodepletion. If 0 DLT/3 or 1 DLT/3 subjects occurs at DL-1, the study will enroll an additional 3 subjects at this dose level. If ≥ 2 DLTs occur at any time, enrollment at this dose level will be stopped. Dose Level 2 (N = 3 to 6): Subjects will receive a single fixed dose of 1 x 108 TmPSMA-02 CAR T cells via IV infusion on Day 0, following lymphodepletion with fludarabine and cyclophosphamide. This dose level will be evaluated as follows: - If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. - If 0 DLT/3 subjects or 1 DLT/6 subjects occur, the study will advance to Dose Level 3 (DL3). - If 2 DLTs occur at any time, enrollment at this dose level will be stopped. If less than 6 subjects were treated at the previous dose level (DL1), additional subjects will be enrolled at that dose level to reach a minimum of 6 DLT-evaluable subjects for MTD determination. • Dose Level 3 (N = 3 to 6): Subjects will receive a single fixed dose of 3 x 108 TmPSMA-02 CAR T cells via IV infusion Day 0, following lymphodepletion with fludarabine and cyclophosphamide. This dose level will be evaluated as follows: - If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. - If 0 DLT/3 subjects occurs, the study will still enroll an additional 3 subjects at this dose level to allow for MTD determination. - If 2 DLTs occur at any time, enrollment at this dose level will be stopped. If less than 6 subjects were treated at the previous dose level (DL2), additional subjects will be enrolled at that dose level to reach a minimum of 6 DLT-evaluable subjects for MTD determination. The highest dose at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects will be declared the MTD. Retreatment Infusions: The Retreatment Phase will remain closed until sufficient safety and persistence data is available in initial subjects, and DSMB and FDA approval to open Retreatment has been received. Subjects who have demonstrated clinical benefit after their initial TmPSMA-02 CAR T cell infusion (e.g., minimum disease response of stable disease, etc.) may also be eligible to receive retreatment with TmPSMA-02 CAR T cells at the physician-investigator's discretion. The TmPSMA-02 retreatment dose administered must either be a) the CAR T cell dose that the subject previously received without DLTs, or b) a CAR T cell dose that is less than or equal to a dose level that has been evaluated for safety in ≥ 3 other subjects without evidence of DLTs. As retreatment infusions will not be used for formal DLT assessments/MTD determination, there are no protocol-defined staggering requirements. ;