A first-in-human Phase 1 study (NCT03873805) evaluated the safety and bioactivity of CAR-T cells directed against prostate stem cell antigens in patients with metastatic castration-resistant prostate cancer.
CancerNetwork® spoke with Saul Priceman, PhD, associate professor and deputy director of Translational Sciences & Technologies in the T Cell Therapeutics Research Laboratories at City of Hope, about the history of the Phase 1 trial and why it was important to conduct such a study.
Priceman noted that the idea for this trial came about 10 years ago when promising results were seen with CAR-T cells in hematologic malignancies and inspired research studying similar responses in solid tumors. Research conducted by City of Hope and supported by the Prostate Cancer Foundation showed minimal side effects from immunotherapy and promising efficacy.
Stabilization of disease according to RECIST was observed in 0% of patients in dose-limiting cohort 1, 67% of patients in dose-limiting cohort 2, and 60% of patients in dose-limiting cohort 3. In addition, the 6-month survival rate in the respective arms was 33%, 67%, and 40%.
No dose-limiting toxicities were observed in cohorts 1 and 3, but 2 patients in cohort 2 experienced them. Cytokine release syndrome (CRS) was also observed in 1 patient in cohort 1, 2 in cohort 2, and 2 in cohort 3. The median time to onset of CRS was 4 days, and there were no grade 3 events.
Transcript:
About 10 years ago, based on the impressive results that were being achieved at the time with chimeric antigen receptor-engineered T cells for hematologic malignancies, we decided to look at whether similar responses could be seen in solid tumors. Prostate cancer was one of the diseases that we were very interested in. With support from the Prostate Cancer Foundation, we began developing a CAR T cell therapy for prostate cancer and came up with prostate stem cell antigen (PSCA) as the tumor antigen we were targeting. Over the course of a series of preclinical laboratory studies, we developed an effective PSCA-targeted CAR T cell therapy. Through a series of funding, largely from the Prostate Cancer Foundation, we again began a Phase 1 clinical trial.
References
Dorff TB, Blanchard SM, Adkins LN, et al. PSCA-CAR T-cell therapy for metastatic castration-resistant prostate cancer: a phase 1 study. Nat Med. 2024;30:1636-1644. doi:10.1038/s41591-024-02979-8
