A multi-center phase 1 dose-escalation trial has evaluated BPX-601, a novel PSCA-targeted CAR T-cell therapy with pharmacological activation by rimiducid, in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and metastatic castration-resistant prostate cancer (mCRPC).
Trial Design and Patient Population
The study (NCT02744287) was conducted across 13 U.S. sites between November 2016 and November 2022. Eligible patients included those with mPDAC showing PSCA expression and disease progression within 6 months of previous treatment, or mCRPC patients with progressive disease according to PCWG2 criteria. The trial employed a 3+3 dose-escalation design with multiple cohorts receiving varying doses of BPX-601 cells and rimiducid.
Treatment Protocol and Modifications
Patients received BPX-601 CAR T-cells following lymphodepletion, with doses ranging from 1.25×106 to 5.0×106 cells/kg. The protocol underwent several modifications to optimize treatment strategies, including:
- Addition of rimiducid (0.4 mg/kg) administration on day 7
- Implementation of weekly rimiducid dosing
- Adjustment of lymphodepletion regimens
- Expansion to include mCRPC patients
Manufacturing and Product Characteristics
The manufacturing process demonstrated high success rates, with 50 out of 51 attempted products successfully manufactured (98% success rate). Key product characteristics included:
- Mean CAR expression: 45.2% for mPDAC and 50.8% for mCRPC products
- Strong cytotoxicity: ~91.5% mean cytotoxicity across both cancer types
- Robust IL-2 production: 5,997-6,870 pg/mL mean levels
Safety and Early Termination
The trial was discontinued early on March 14, 2023, following two dose-limiting toxicity events in the ongoing cohort. Despite early termination, the study provided valuable insights into the safety profile and potential efficacy of the BPX-601 platform.
Clinical Implications
The study represents a significant step forward in CAR T-cell therapy for solid tumors, introducing several innovative features:
- First-in-human evaluation of pharmacologically regulated CAR T-cells targeting PSCA
- Novel approach using rimiducid for controlled T-cell activation
- Demonstration of manufacturing feasibility for solid tumor CAR T-cell therapy
Biomarker Analysis and Monitoring
The trial incorporated comprehensive biomarker analyses, including:
- PSCA expression screening for patient selection
- Vector copy number tracking for CAR T-cell persistence
- Serum cytokine profiling
- Tissue analysis using chromogenic in situ hybridization
