CAR T-Cell Therapy Demonstrates Feasibility in Resistant Prostate Cancer

Mustang Bio’s prostate stem cell antigen (PSCA)-targeted chimeric antigen receptor (CAR) T-cell therapy MB-105 has demonstrated feasibility in metastatic castration-resistant prostate cancer mCRPC.^1,2

New data from the phase 1 trial (NCT03873805) evaluating MB-105 were presented at the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium February 17 - 19, 2022, San Francisco, California, by Tanya B. Dorff, MD, medical oncologist and researcher, City of Hope Cancer Center.

The trial has treated 12 patients (median age, 68 years [range, 42-72])so far at City of Hope, some of whom were treated with lymphodepletion chemotherapy. At a level of 100 million cells, not much preliminary efficacy was seen with lymphodepletion chemotherapy but once fludarabine and cyclophosphamide were added, 2 patients experienced grade 3 dose-limiting toxicities (DLTs) of non-infective cystitis and fatigue. This led investigators to modify protocols to reduce cyclophosphamide dose and to closely monitor for cystitis.

Three patients have been treated in the modified lymphodepletion 100 million cell cohort with no DLTs. Low grade (≤ grade 2) cytokine release syndrome occurred in 4 patients. Preliminary efficacy assessments revealed 7 patients with stable disease and 5 with progressive disease via Response Evaluation Criteria in Solid Tumors (RECIST). Patients had measurable declines in prostate antigen (PSA) as well as radiographic improvement, with 1 patient exhibiting a 90% decline in PSA. Investigators also observed bioactivity of PSCA CAR T-cells.

READ MORE: Memory T Cell CAR T Therapy Showcases Anti-Tumor Activity in Resistant Prostate Cancer

“We've found that PSCA targeted CAR t-cell therapy is safe and can be effective preliminarily in men with mCRPC. There’s clearly more work to be done and we’re preparing a phase 1B trial to further study some different dosing strategies to optimize efficacy and minimize toxicity. The DLT of cystitis is likely on-target, off-tumor effects due to PSC expression in the bladder and that’s something that we’ll work hard to mitigate moving forward,” Dorff said during her presentation.¹

The trial will continue to enroll up to 33 patients and dose-escalation will continue up to the next dose level of 300 million cells. The trial’s primary endpoints are safety and dosing and include secondary endpoints of expansion and persistence of PSCA CAR T-cells, clinical response via Prostate Cancer Working Group 3 criteria, survival outcomes, and serum cytokine profiles in peripheral blood pre- and post-therapy. Secondary endpoints will also describe PSCA expression level on tumor cells before and after CAR T-cell infusion, disease response, and toxicities.

“The Phase 1 data... demonstrate the potential of Mustang’s MB-105 as a PSCA-targeted CAR T-cell therapy for prostate cancer. There is a potential to apply this therapy in other solid tumors that express PSCA. We remain encouraged by the ongoing progress of this trial as we develop our pipeline of cell therapy treatments for patients with cancers that are difficult to treat,” Manuel Litchman, MD, president and chief executive officer, Mustang Bio, said in a statement.²

REFERENCES

1. 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). Presented at: 2022 ASCO GU Symposium, February 17-19, San Francisco, California.
2. Mustang Bio announces City of Hope MB-105 prostate stem cell antigen CAR T data selected for presentation at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium. News release. Mustang Bio. February 15, 2022. https://www.globenewswire.com/news-release/2022/02/15/2385111/0/en/Mustang-Bio-Announces-City-of-Hope-MB-105-Prostate-Stem-Cell-Antigen-CAR-T-Data-Selected-for-Presentation-at-the-2022-American-Society-of-Clinical-Oncology-Genitourinary-Cancers-Sy.html