Assessing the Benefit of CAR T-cell Therapies for mCRPC

A first-in-human phase 1 trial (NCT03873805) investigated the safety and bioactivity of prostate stem cell antigen-directed CAR T cells for patients with metastatic castration-resistant prostate cancer.

CancerNetwork® spoke with Saul Priceman, PhD, associate professor and associate director of the 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 a trial like this.

Priceman noted the idea for this trial began 10 years ago when promising results were observed with CAR T-cells in hematologic malignancies inspired research that evaluated similar responses in solid tumors. Research conducted by City of Hope, as well as support from the Prostate Cancer Foundation, revealed minimal adverse effects from the immunotherapy, and promising activity.

Stable disease by RECIST was observed in 0% in the dose-limiting cohort 1, 67% in the dose-limiting cohort 2, and 60% in the dose-limiting cohort 3. Additionally, the 6-month survival rate in each respective arm was 33%, 67%, and 40%.

In cohort 1 and 3, there were no dose-limiting toxicities observed, 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 was no grade 3 severity.

Transcript:

It was about 10 years ago, we decided that because of the impressive results that were occurring at the time with chimeric antigen receptor engineered T-cells for hematologic malignancies, we moved into addressing whether similar responses could be seen in solid tumors. Prostate cancer was a big disease on our minds. We’ve begun research around developing a CAR T-cell therapy for prostate cancer with support from Prostate Cancer Foundation and landed on prostate stem cell antigen [PSCA] as the tumor antigen that we were targeting. Over a series of preclinical laboratory studies, [we] developed a potent PSCA-directed CAR T cell therapy. Through a series of funding largely through Prostate Cancer Foundation, again, we embarked on a phase 1 clinical trial.

References

Dorff T B, Blanchard S M, Adkins L N, et al. PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat Med. 2024;30:1636-1644. doi:10.1038/s41591-024-02979-8