A primary-in-human section 1 trial (NCT03873805) investigated the security and bioactivity of prostate stem cell antigen-directed CAR T cells for sufferers with metastatic castration-resistant prostate most cancers.
CancerNetwork® spoke with Saul Priceman, PhD, affiliate professor and affiliate director of the Translational Sciences & Applied sciences within the T Cell Therapeutics Analysis Laboratories at Metropolis of Hope concerning the historical past of the section 1 trial and why it was vital to conduct a trial like this.
Priceman famous the thought for this trial started 10 years in the past when promising outcomes had been noticed with CAR T-cells in hematologic malignancies impressed analysis that evaluated related responses in stable tumors. Analysis carried out by Metropolis of Hope, in addition to assist from the Prostate Most cancers Basis, revealed minimal hostile results from the immunotherapy, and promising exercise.
Steady illness by RECIST was noticed in 0% within the dose-limiting cohort 1, 67% within the dose-limiting cohort 2, and 60% within the dose-limiting cohort 3. Moreover, the 6-month survival charge in every respective arm was 33%, 67%, and 40%.
In cohort 1 and three, there have been no dose-limiting toxicities noticed, however 2 sufferers in cohort 2 skilled them. Cytokine launch syndrome (CRS) was additionally noticed in 1 affected person in cohort 1, 2 in cohort 2, and a couple of 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 in the past, we determined that due to the spectacular outcomes that had been occurring on the time with chimeric antigen receptor engineered T-cells for hematologic malignancies, we moved into addressing whether or not related responses may very well be seen in stable tumors. Prostate most cancers was an enormous illness on our minds. We’ve begun analysis round growing a CAR T-cell remedy for prostate most cancers with assist from Prostate Most cancers Basis and landed on prostate stem cell antigen [PSCA] because the tumor antigen that we had been focusing on. Over a collection of preclinical laboratory research, [we] developed a potent PSCA-directed CAR T cell remedy. By means of a collection of funding largely via Prostate Most cancers Basis, once more, we launched into a section 1 medical trial.
References
Dorff T B, Blanchard S M, Adkins L N, et al. PSCA-CAR T cell remedy in metastatic castration-resistant prostate most cancers: a section 1 trial. Nat Med. 2024;30:1636-1644. doi:10.1038/s41591-024-02979-8
