Tanya Dorff, MD, Speaks to the Development of CAR T-Cell Therapy in Prostate Cancer

CAR T cells are typically used in the treatment of hematologic malignancies, but recent studies have shown they may also be used to combat prostate cancer. A recent panel discussion by Tanya Dorff, MD, from the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting shed light on this potential addition to the prostate cancer treatment paradigm.

Several trials are underway assessing the use CAR T cells targeted to prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), and KLK2. Dorff emphasized the importance of educating oncologists who treat solid malignancies to identify adverse effects and mechanisms associated with CAR T-cell therapies that those specializing in hematologic malignancies may be more familiar with.

“A big part of our education focus was just to help familiarize solid tumor oncologists with things like cytokine release syndrome and macrophage activation and the ways these present and how to manage them. That’s the long-term implementation of making sure the community is educated as a whole so these treatments can be widely accessed,” Dorff, an associate professor in the Department of Medical oncology and Therapeutics Research, and section chief of the Genitourinary Disease Program at City of Hope, said in an interview with CancerNetwork^®.

Dorff also discussed highlights in prostate cancer from the 2022 ASCO Annual Meeting, including the use potential treatment intensification with triplet regimens up front and the efficacy of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

CancerNetwork^®: Can you provide a brief overview of the CAR T-cell panel discussion you participated in at this year’s meeting?

Dorff: I was part of an educational session discussing CAR T-cell therapy and bispecific T-cell engaging therapy for advanced prostate cancer. It was a case-based approach helping oncologists get a sense of how these treatments that are traditionally used in hematologic malignancies are being studied in prostate cancer, what to expect from them, how things are going, what kind of results we’re seeing, and where we’re going next with the field.

What does the future of CAR T look like for prostate cancer?

We have a long way to go to get CAR T-cell therapy into practice for prostate cancer, but we’ve been excited that even within the first handful of patients treated on the various trials, we are seeing responses. At the 2022 ASCO Genitourinary Symposium (ASCO GU), a poster was presented for POSEIDA’s PSMA CAR T product by Susan F. Slovin, MD, PhD, of Memorial Sloan Kettering,¹ showing this beautiful response in a patient and a fairly robust PSA [prostate specific antigen] response waterfall from that early experience with the CAR T-cell [study. Findings using] our PSCA-targeted CAR T from City of Hope that our scientists have developed and we produce here were also presented a ASCO GU showing, again, a robust response early on. However, the toxicity was considerable.² We’re just learning what the [adverse] effect [AE] profile will look like in [patients with] prostate cancer vs hematologic malignancies. Taking a step back, we’re still sorting out optimal dosing and whether we’re going to need adjunctive strategies or multiple doses to get a higher rate of nice, durable remissions with these therapies.

Are there any other ongoing trials assessing the use CAR T-cell therapy in prostate cancer?

Multiple trials are open and accruing. We have 3 of them open here at City of Hope, 1 with our own PSCA-targeted CAR T-cell product. We’re just finishing up phase 1 study and expect to open the phase 1b study later this summer where we’re going to be testing multiple dosing and radiation prior to CAR T-cell administration, which in the lab seems to augment responsiveness; a good number of patients already have been treated. The PSMA targeted CAR T from POSEIDA is still accruing. We’ve treated 7 [patients] here. It’s a multi-site study, so there are many other sites that have treated patients as well, and that’s still ongoing. Then there's the KLK2 targeted CAR T-cell study [NCT04898634] from Janssen. That’s a little earlier along but they’ve treated a fair number of patients at this point; it’s a multicenter study. This is already a reality in terms of clinical trials, but still far from practice.

What were some of the key studies that read out in the prostate cancer space at the 2022 ASCO Annual Meeting?

There are 2 big topics that came out of ASCO for prostate cancer this year. One was the up-front intensification study using triplet combinations where we’re not only adding chemotherapy up front or an androgen targeted agent like abiraterone [Yonsa], enzalutamide [Xtandi], apalutamide [Erleda], or darolutamide [Nubeqa], but using all the above. The important message to get out is for community oncologists and urologists to act on this and implement this in their own practices. Newly diagnosed [patients with] metastatic prostate cancer should not get just castration monotherapy. They will benefit tremendously from having up-front intensification with either doublet or in some cases triplet therapy.

The other big story is the 177Lu-PSMA-617 which was recently approved by the FDA based on the [phase 3] VISION trial [NCT03511664].³ There’s a lot of information coming out at some of these meetings about differences between the VISION trial and the [phase 2] TheraP trial [NCT03392428], in which the control arm was cabazitaxel [Jevtana], which helps us benchmark the efficacy and start to think about sequencing. Also, what PSMA PET characteristics might help us optimally select patients for this treatment, because the criteria have been different [across] trials. There has been all kinds of practical and helpful information presented at ASCO and a lot of buzz and talking among attendees about those topics.

References

1. Slovin SF, Dorff TB, Falchook GS, et al. Phase 1 study of P-PSMA-101 CAR-T cells in patients with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. February 16, 2022;40(suppl 6):98. doi:10.1200/JCO.2022.40.6_suppl.098
2. Dorff TB, Blanchard S, Martirosyan H, et al. Phase 1 study of PSCA-targeted chimeric antigen receptor (CAR) T cell therapy for metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. February 16, 2022;40(suppl 6):91. doi:10.1200/JCO.2022.40.6_suppl.091
3. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. News Release. March 23, 2022. Accessed September 7, 2022. https://bit.ly/3BlvV76