Tanya B. Dorff, MD, on Results From Phase 1 CAR T-Cell Therapy mCRPC Trial

Commentary
Video

Findings from a phase 1 study may inform future trial designs intended to yield longer responses with PSCA-targeted CAR T cells.

Tanya B. Dorff, MD, professor in the Department of Medical Oncology and Therapeutics Research and division chief of the Genitourinary Disease Program at City of Hope in Duarte, California, spoke with CancerNetwork® about the results of a phase 1 trial (NCT03873805) evaluating the efficacy and adverse effects (AEs) of prostate stem cell antigen (PSCA)–directed CAR T cells in metastatic castration-resistant prostate cancer (CRPC).

According to Dorff, there were reports of limited activity with study treatment in one cohort as well as augmented AEs in another. In a third cohort, PSCA-targeted CAR T cells elicited clinical improvements in prostate cancer without an increased risk of serious AEs. Although investigators did not report long-acting responses, the results will serve as the basis for designing future trial phases that aim to elicit frequent and longer responses.

Transcript:

This was a phase 1 first-in-human trial, and as such, one of the main goals was to understand how these CAR T cells would behave, both in terms of whether they tracked to the tumor and created anti-cancer efficacy, but also what the [adverse] effects would be because we know this is a very powerful form of immunotherapy. We initially treated patients just with the CAR T cells and saw limited activity, and then we added the standard lympho-depletion chemotherapy, which is used when CAR T cells are used in hematologic malignancies, and that did augment the efficacy but also the [adverse] effects. We had to create a third cohort, which was not exactly what we expected to do; we expected to just escalate the dose of the T cells that we were infusing where we modified the lympho-depletion chemotherapy. With that, we found that we could safely administer the PSCA-targeted CAR-T cells, and we did have several patients who responded who had clinical improvement in their cancer by PSA and/or by imaging. [However], the CAR T-cells weren't staying active as long as we would have hoped. They weren't persisting, and we didn't cure anyone in this very first very small trial. But we learned a lot that's going to help us design the next phases of study where we hope that we can start to see more significant, more frequent, and longer lasting responses.

Reference

Dorff TB, Blanchard SM, Adkins LN, 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

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