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 Tanya B. Dorff, MD, professor within the Division of Medical Oncology and Therapeutics Analysis and division chief of the Genitourinary Illness Program at Metropolis of Hope in Duarte, California, about what she hopes colleagues will take away from the outcomes of the trial.
Dorff highlighted the anticancer impact and security of CAR T-cell remedy inside this trial. Security was emphasised by contrasting different trials with extreme toxicities with minimal opposed results noticed on this trial. Dorff famous that information gained from observing the exercise of CAR T cells on this trial and others have superior their understanding of CAR T-cell pharmacokinetics.
Dorff expressed hoping to study extra about sufferers probably to profit from CAR T-cell remedy. By understanding affected person traits, therapy improvement progress will speed up.
Secure illness by RECIST standards was noticed in 0% of sufferers in cohort 1, 67% in cohort 2, and 60% in cohort 3. Moreover, the 6-month survival fee in every respective arm was 33%, 67%, and 40%.
In cohorts 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 have been no grade 3 instances of CRS.
Transcript:
Crucial message is that this remedy can work. In our trial, we did have sufferers who had vital proof of anticancer impact, and it may be achieved safely. That is additionally necessary as a result of, once more, in a number of the different trials, there have been some extreme toxicities which may dampen enthusiasm. It is all about understanding the kinetics, tips on how to make the T cells highly effective and proliferative, however not an excessive amount of. Studying from this, in addition to a number of the different medical trials in prostate most cancers with completely different sorts of CAR T cells, we have actually made a big advance in our understanding. We’re additionally hoping to study extra about what sorts of sufferers would possibly profit [and] what kinds of tumor traits or innate host immune traits [they have], as a result of it is at all times higher to have the ability to choose the sufferers probably to profit, which is able to assist speed up the progress in growing this therapy.
References
Dorff TB, Blanchard SM, Adkins LN, 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
