Phase 1 Study Examines CAR T Cells in Metastatic Castration-Resistant Prostate Cancer

Tanya Dorff, MD, a medical oncologist, section chief of Genitourinary Disease Program, and associate professor in the Department of Medical Oncology & Therapeutics Research at City of Hope, discusses the design and methods used in the phase 1 study (NCT03873805) of chimeric antigen receptor (CAR) T-cell therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

The study looks to evaluate the side effects and best dose of prostate stem cell antigen (PSCA)-CAR T cells in 33 patients with prostate stem cell antigen positive mCRPC. Patients enrolled were planned to receive a starting dose of PSCA-targeted 4-1BB-co-stimulated CAR T cell therapy at 100 million without lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide. Then, if deemed safe, lymphodepletion chemotherapy would be added to the 100 million prior to dose escalation to maximum 600 million. 

Primary end points of the trial include to determine the full toxicity profile of the novel CAR T cells and the dose-limiting toxicities with secondary end points including assessment of persistence and expansion of CAR T cells, disease response, overall survival, progression-free survival, PSCA expression, and serum cytokine profile.

Transcription:

0:08 | Our design was to start with just 100 million CAR T cells. We produce them very similarly to the FDA-approved leukemia and lymphoma CAR T cells. We do a leukapheresis, we use a viral transfection to change what the T-cell receptor is targeting, and then we produce hundreds of millions of cells. The process is the same, it's just different what we are targeting the CAR T cells to.

0:35 | We decided to start out with just the cells, and then if that looked safe, then we could add in the lymphodepleting chemotherapy. Traditionally with CAR T cells in leukemia and lymphoma, they give cyclophosphamide and fludarabine. We weren't sure whether that would be necessary when we were translating this to solid tumors because the solid tumor is not in the space where leukemia and lymphoma reside.

1:03 | It turns out that it's important to use lymphodepletion, it seems to increase the ability of the CAR T cells to work, but it probably does it by a very different mechanism in this disease. We were planning to add in the lymphodepletion, keeping the dose at 100 million cells, and then try to escalate to 300 million and 600 million CAR T cells.