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

Commentary
Video

A phase 1 trial assessed the use of PSCA-directed CAR T cells in patients with metastatic castration-resistant prostate cancer.

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 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, about what she hopes colleagues will take away from the results of the trial.

Dorff highlighted the anticancer effect and safety of CAR T-cell therapy within this trial. Safety was emphasized by contrasting other trials with severe toxicities with minimal adverse effects observed in this trial. Dorff noted that knowledge gained from observing the activity of CAR T cells in this trial and others have advanced their understanding of CAR T-cell pharmacokinetics.

Dorff expressed hoping to learn more about patients most likely to benefit from CAR T-cell therapy. By understanding patient characteristics, treatment development progress will accelerate.

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

In cohorts 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 were no grade 3 cases of CRS.

Transcript:

The most important message is that this therapy can work. In our trial, we did have patients who had significant evidence of anticancer effect, and it can be done safely. That's also important because, again, in some of the other trials, there have been some severe toxicities that might dampen enthusiasm. It's all about understanding the kinetics, how to make the T cells powerful and proliferative, but not too much. Learning from this, as well as some of the other clinical trials in prostate cancer with different kinds of CAR T cells, we've really made a significant advance in our understanding. We're also hoping to learn more about what kinds of patients might benefit [and] what sorts of tumor characteristics or innate host immune characteristics [they have], because it's always better to be able to select the patients most likely to benefit, which will help accelerate the progress in developing this treatment.

References

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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