Activity of 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 Comprehensive Cancer Center, discusses the recent findings from a phase 1 clinical trial (NCT03873805) which explored the use of chimeric antigen receptor (CAR) T-cell therapy in patients with prostate cancer.

The study aims to evaluate 33 patients with metastatic castration-resistant prostate cancer (mCRPC). The primary end point is to determine the full toxicity profile of the novel CAR T cells as well as the dose-limiting toxicities with secondary end points consisting of persistence of CAR T cells, expansion of CAR T cells, disease response, overall survival, progression-free survival, prostate stem cell antigen (PSCA) expression, and serum cytokine profile.

Preliminary findings of the study were presented during the American Society of Oncology Genitourinary Cancers Symposium and revealed that of the 12 patients treated, there was some activity seen from CAR T cells alone, including a 95% reduction in PSA, radiographic, and circulating tumor cell response. Additionally, PSCA CAR T cells were shown to be able to induce an anti-tumor effect with a dose of 100 million CAR T cells or higher.

Transcription:

0:08 | We've treated 12 patients, and things didn't go exactly according to plan. We did see some activity of the CAR T cells alone, which was exciting, but not big durable responses. When we added in the lymphodepletion, we did see some very dramatic responses. One of them was a 95% reduction in PSA as well as radiographic response and circulating tumor cell response. We looked at this patient's disease and it was clearly significantly reduced by the CAR T cells.

0:42 | Then, we show another patient who was a responder with liver metastases, but we did hit a dose-limiting toxicity of cystitis. Because PSCA is expressed on the bladder, the CAR T cells were causing irritation inflammation in the bladder. Instead of dose escalating, we had to expand at the same dose level. In fact, we wanted to avoid having this side effect because it's symptomatic for patients. We reduced the dose of the chemotherapy, which we figured was probably contributing to the severity. And so far, it seems like that was correct.

1:20 | With the lower-dose chemotherapy and 100 million CAR T cells, we're not seeing the severe cystitis. We have still seen responsiveness against the cancer. We're just going to finish this out and then we want to move into more of a phase 1B to explore some different dosing strategies that we think will optimize efficacy versus toxicity.