The FDA lifted a partial clinical hold on the phase 1 P-PSMA-101-001 clinical trial of the chimeric antigen receptor T product P-PSMA-101, which is a potential treatment for patients with metastatic castration-resistant prostate cancer.
The FDA has lifted a partial clinical hold on the phase 1 P-PSMA-101-001 clinical trial (NCT04249947) of the chimeric antigen receptor (CAR) T product P-PSMA-101, which is a potential treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The trial will continue immediately, announced Poseida Therapeutics, Inc.1
The FDA placed the partial clinical hold in August 2020, on enrollment while a patient death was investigated per study protocol. The patient, who had mCRPC, failed treatment with multiple prior lines of anti-cancer therapies and was given P-PSMA-101 as treatment in late July. The patient had normal lab results and no clinical symptoms during the first week post-treatment but missed both the day 10 and day 14 follow-up visits. The patient developed symptoms that subsequently led to hospitalization during this time and died due to hepatic failure at day 19.2
The direct cause of the hepatic failure was not confirmed, but the patient had developed symptoms consistent with macrophage activation syndrome, which is a serious and potentially fatal overactivation of the immune system that is often associated with CAR T-cell therapies. It is also known to have other causes, such as infection or autoimmune disease. The patient had also developed blurred vision, which was confirmed as uveitis.
The company agreed to implement protocol amendments, which are intended to increase patient compliance and safety, such as inclusion of modified inclusion and exclusion criteria and frequency of monitoring and laboratory testing. This is the first CAR T therapeutic candidate for solid tumors from the company.
P-PSMA-101 is an autologous CAR T-cell therapy that has been designed to target prostate-specific member antigen (PSMA) expressed on mCRPC cells. The study was developed utilizing the company’s proprietary piggyBac DNA Modification System, which produces product candidates with a high percentage of stem cell memory T cells.
The study was initiated in May 2020 and is an open-label, multicenter, dose-escalating trial aimed to determine the optimal dose of the CAR T-cell therapy. The primary end points include the safety of P-PSMA-101, maximum tolerated dose, and efficacy. P-PSMA-101 was given in either single or multiple doses across patient cohorts in the study.
In order to be included in the study, patients had to have mCRPC that continues to grow despite prior treatment for advanced disease, recovered from serious AEs from any prior therapies, and have adequate organ function within predetermined parameters and an ECOG performance status of either 0 or 1 to be eligible to enroll in the study.
Patients were ineligible for the study if they had inadequate venous access and/or contraindications to leukapheresis, an active second malignancy beyond mCRPC, active autoimmune disease, a history of significant central nervous system disease, an active systemic infection, or have received anticancer therapies within 2 weeks of the conditioning chemotherapy initiation. Patients were also excluded from enrollment if they had received immunosuppressive medications within 2 weeks of initiating leukapheresis or have received systemic corticosteroid therapy.
1. Poseida Therapeutics Announces Clinical Hold Lifted on Phase 1 Autologous CAR-T Study in Prostate Cancer. News Release. November 2, 2020. Accessed November 2, 2020. https://prn.to/3kPjlCp
2. Form 8-L: Poseida Therapeutics, Inc. United States Securities Exchange Commission. August 17, 2020. Accessed November 2, 2020. https://bit.ly/2CEl4cR