Tanya Dorff, MD, talks about the development of CAR T-Cell therapy in prostate cancer

At ASCO 2022, Tanya Dorff, MD, reviewed the use of CAR T cells in the treatment of prostate cancer.

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

Several trials are underway to evaluate the use of 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 with which hematological malignancies specialists may be more familiar.

“A lot of our training focus was just to help solid tumor oncologists learn about things like cytokine release syndrome and macrophage activation and how they present and how manage them. It’s the long-term implementation of making sure the community is educated as a whole so that these treatments are widely available,” Dorff, associate professor in the Department of Medical Oncology and Therapeutic Research, and Section Head of the Genitourinary Diseases Program at City of Hope, said in an interview with CancerNetwork®.

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

Cancer Network®: Can you give a brief overview of the CAR T-cell roundtable you participated in at this year’s meeting?

Dorff: I participated in an educational session on CAR T-cell therapy and bispecific therapy involving T-cells for advanced prostate cancer. This was a case-based approach helping oncologists understand how these treatments traditionally used in hematological malignancies are studied in prostate cancer, what to expect from them, how things work, what kinds of results we see, and where we’re going next with the field.

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

We still have a long way to go to put CAR T-cell therapy for prostate cancer into practice, but we are delighted that even among the first handful of patients treated in 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 nice response in a patient and quite robust PSA [prostate specific antigen] response cascade of this first experience with the CAR T-cell [study. Findings using] our City of Hope PSCA targeted CAR T that our scientists developed and are producing here was also featured an ASCO GU showing, again, a robust response early on. However, the toxicity was considerable.2 We just learn what [adverse] effect [AE] the profile will look like [patients with] prostate cancer vs hematological malignancies. Looking back, we are still determining the optimal dosage and whether we will need add-on strategies or multiple doses to achieve a higher rate of pleasant and lasting remissions with these therapies.

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

Multiple trials are open and accumulate. We have 3 open here at City of Hope, 1 with our own PSCA targeted CAR T-cell product. We have just completed the phase 1 study and plan to open the phase 1b study later this summer, where we will test multiple dosages and radiation prior to CAR T-cell administration, which in the lab appears to be increasing the reactivity ; many patients have already been treated. POSEIDA’s CAR T-targeted PSMA continues to accumulate. We treated 7 [patients] here. This is a multi-site study, so there are many other sites that have also treated patients, and it’s still ongoing. Then there’s the KLK2-targeted CAR T cell study [NCT04898634] by Janssen. It’s a bit earlier, but they’ve treated a good number of patients at this point; it is 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 were read about in the area of ​​prostate cancer at the 2022 ASCO Annual Meeting?

There are 2 big topics that came out of the ASCO for prostate cancer this year. One was the initial intensification study using triplet combinations where we don’t just add upstream chemotherapy or an androgen targeting agent like abiraterone [Yonsa]enzalutamide [Xtandi]apalutamide [Erleda]or darolutamide [Nubeqa], but using all of the above. The important message to get across is that community oncologists and urologists act accordingly and implement this in their own practices. Newly Diagnosed [patients with] metastatic prostate cancer should not receive castration monotherapy alone. They will benefit tremendously from initial intensification with dual therapy or, in some cases, triple therapy.

The other big story is 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 the differences between the VISION trial and the trial. [phase 2] TheraP trial [NCT03392428]in which the control arm was cabazitaxel [Jevtana], which helps us compare efficiency and start thinking about sequencing. Also, what characteristics of PSMA PET could help us to optimally select patients for this treatment, as the criteria have been different [across] trials. There was all kinds of practical and useful information presented at ASCO and a lot of buzz and discussion among attendees on these 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. 2022 Feb 16;40(supplement 6):98. doi:10.1200/JCO.2022.40.6_suppl.098
  2. Dorff TB, Blanchard S, Martirosyan H, et al. Phase 1 study of chimeric antigen receptor (CAR) T cell therapy targeting PSCA for metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2022 Feb 16;40(supplement 6):91. doi:10.1200/JCO.2022.40.6_suppl.091
  3. The FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. Press release. March 23, 2022. Accessed September 7, 2022. https://bit.ly/3BlvV76

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