FDA Halts Phase 1 Trial With P-PSMA-101 in mCRPC Following Patient Death


The FDA has placed a clinical hold on the phase 1 P-PSMA-101-001 trial examining the autologous CAR T-cell therapy P-PSMA-101 in patients with metastatic castration-resistant prostate cancer.

The FDA has placed a clinical hold on the phase 1 P-PSMA-101-001 trial (NCT04249947) examining the autologous CAR T-cell therapy P-PSMA-101 in patients with metastatic castration-resistant prostate cancer (mCRPC), following a notification of a patient death that had been issued by Poseida Therapeutics, Inc, the developer of the product.1

The patient, who had previously progressed on several anticancer drugs before receiving treatment with the CAR T-cell product in late July 2020, was reported to have had normal laboratory results following the first 7 days of treatment, with no clinical symptoms indicative of an adverse effect (AE).

However, the patient went on to miss his follow-up visits slated for day 10 and day 14. During that time, he went on to develop symptoms that led to hospitalization. The patient died of hepatic failure on day 19 post treatment with P-PSMA-101.

Notably, to date, the direct cause of the hepatic failure has not been confirmed. The patient was reported to have presented with symptoms that are consistent with macrophage activation syndrome (MAS), which is a serious overactivation of the immune system that has been linked with CAR T-cell therapies. However, MAS can also be caused by other events, such as infection or autoimmune disease.

Moreover, the patient was also reported to have developed blurred vision, and subsequently received a diagnosis of uveitis. Per investigator assessment, the severe toxicity was found to potentially be associated with the CAR T-cell product; however, this will be investigated further.

To date, no other patients on the study have reported severe AEs of decreased vision, uveitis, MAS, or hepatic failure. No cases of cytokine release syndrome or neurotoxicity have been reported either.

“The Company’s assessment of the event and evaluation of next steps is ongoing, including assessment of protocol changes, if any, as indicated by the findings,” Mark J. Gergen, president and chief business officer of Poseida, stated in a report. “The Company is awaiting a formal response from the FDA and is preparing recommendations designed to allow resumption of the clinical study of P-PSMA-101 may be resumed.”

P-PSMA-101 was developed to target prostate-specific membrane antigen, which is expressed on mCRPC cells, according to Poseida.2 The product was created using the company’s piggyBac DNA Modification System, which manufactures products with a high percentage of stem cell memory cells; these cells possess the potential to reconstruct the entire spectrum of T cell subsets, including effecter T cells, which play an instrumental role in tumor killing. The higher composition of stem cell memory cells is believed to be key to addressing challenges linked with earlier-generation CAR T-cell products, according to Poseida.

In the open-label, multicenter, dose-escalating, phase 1 trial, investigators set out to determine the optimal dose of P-PSMA-101 that can be administered safely in patients with mCRPC.3 To be eligible for participation, patients had to have mCRPC that continues to grow, despite previous treatment for advanced disease; they also had to recover from serious AEs experienced with prior therapies. Patients had to have adequate organ function within predetermined parameters and an ECOG performance status of 0 or 1.4

Patients who had inadequate venous access and/or contraindications to leukapheresis, had 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 conditioning chemotherapy initiation, were not permitted. Patients also could not have received immunosuppressive medications within 2 weeks of initiating leukapheresis or have received systemic corticosteroid therapy in that time.

The primary end points of the trial are examining the safety of the product, determining the maximum-tolerated dose, and evaluating the efficacy of P-PSMA-101. In the trial, patient cohorts received either single or multiple doses of the product. Poseida announced that the first patient had received treatment on May 20, 2020.

Poseida is also in the process of developing an off-the-shelf CAR T-cell product, referred to as P-PSMA-ALLO1.


  1. Gergen MJ. Form 8-L: Poseida Therapeutics, Inc. United States Securities Exchange Commission. August 17, 2020. Accessed August 18, 2020.
  2. Poseida Therapeutics announces dosing of first patient on phase 1 clinical trial of P-PSMA-01 autologous CAR-T for metastatic castration-resistant prostate cancer. News release. Poseida Therapeutics, Inc. May 20, 2020. Accessed August 18, 2020.
  3. A phase I study of P-PSMA-01 CAR T-cell therapy in men with metastatic castration-resistant prostate cancer. Memorial Sloan Kettering Cancer Center. Accessed August 18, 2020.
  4. P-PSMA-01 CAR-T cells in the treatment of subjects with metastatic castration-resistant prostate cancer (mCRPC). Updated July 13, 2020. Accessed August 18, 2020.
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