Hold Lifted on Phase 1 Trial Testing P-PSMA-101 CAR T-cell Therapy in mCRPC

Hold Lifted on Phase 1 Trial Testing P-PSMA-101 CAR T-cell Therapy in mCRPC

A Phase 1 trial evaluating Poseida Therapeutics’ autologous CAR T-cell therapy P-PSMA-101 for metastatic castration-resistant prostate cancer (mCRPC) is resuming immediately, after its clinical hold was lifted.

The U.S. Food and Drug Administration (FDA) had placed a partial hold on the trial in August, after a patient died of liver failure a few weeks after receiving the therapy.

Poseida will now implement changes to its protocol to enhance patient compliance and safety, including modified criteria for patient inclusion and exclusion in the trial, and more frequent monitoring, the company announced in a press release.

P-PSMA-101 is a type of immunotherapy in which a patient’s own T-cells — immune cells with anti-tumor activity — are collected and genetically modified in the lab to better fight cancer, and then are expanded and infused back into the patient.

Specifically, P-PSMA-101 contains T-cells engineered to produce a man-made chimeric antigen receptor, or CAR, that helps them recognize and kill cells containing the prostate-specific membrane antigen (PSMA) — a protein found at high levels on the surface of prostate cancer cells — while leaving healthy cells unharmed.

Previous studies suggested that P-PSMA-101 outperformed other PSMA-targeted CAR T-cell therapies. Unlike most of the other therapies, a unique feature of P-PSMA-101 is the fact it does not use a virus to carry the new genetic material to T-cells. Also, most of its CAR T-cells are stem cell memory T-cells, which is believed to enhance the treatment durability.

The ongoing trial (NCT04249947) is evaluating the safety and effectiveness of P-PSMA-101 in about 40 adult patients with mCRPC whose disease progressed after at least one prior line of treatment. Recruitment is ongoing at multiple sites in the U.S.

Participants will receive ascending doses of P-PSMA-101, in either a single dose or multiple administrations. After undergoing a round of chemo — to prevent the patient’s immune system from reacting to the cells in P-PSMA-101 — participants will receive the therapy via intravenous (into-the-vein) infusions.

The aim is to help determine the optimal dose for further testing.

The trial started dosing patients in May, but the FDA decided to pause its enrollment after a patient died soon after receiving P-PSMA-101. The patient had failed to respond to several other anti-cancer therapies before joining the study.

Within the first seven days after dosing, the patient’s lab tests were normal, and there were no signs of an adverse event. However, the patient missed his follow-up visits on days 10 and 14, during which time he developed symptoms that eventually led to hospitalization. The patient died of liver failure at day 19 post-treatment.

While the cause of liver failure was unknown, the patient’s symptoms were consistent with macrophage activation syndrome — a life-threatening condition caused by excessive activation and proliferation of certain white blood cells. This reaction is often associated with CAR T-cell therapies, but can have other causes, such as infections or autoimmune diseases.

The patient had also developed blurred vision, which was diagnosed as uveitis. According to the company’s report, neither of these serious adverse events had been reported in any other patient receiving this treatment.