ASCO GU 2022: Phase 1 Study of P-PSMA-101 CAR-T Cells in Patients With Metastatic Castration-Resistant Prostate Cancer

(UroToday.com) On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, Poster Session A focused on the care of patients with prostate cancer. Dr. Slovin presented a poster on a phase 1 trial examining the use of P-PSMA-101, a chimeric antigen receptor T (CART) therapy targeting PSMA for men with advanced prostate cancer. P-PSMA-101 is an autologous CAR-T therapy targeting PSMA, with a high percentage of stem cell memory T cells (TSCM) associated with efficacy, safety, and bone homing (particularly relevant to prostate cancer). P-PSMA-101 is manufactured using a novel non-viral transposon system (piggyBac) that creates high TSCM products.

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In preclinical mouse models of prostate cancer, P-PSMA-101 completely eliminated tumors.

In this phase 1 trial (NCT04249947), the authors enrolled patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with or not eligible for a CYP17 inhibitor or second-generation antiandrogen and a taxane and who had measurable disease and adequate organ function. Patients with secondary malignancies, active infection, or significant autoimmune, central nervous system, cardiac, ocular or liver disease were excluded. P-PSMA-101 was manufactured from apheresed T cells and administered IV following a standard 3-day cy/flu lymphodepletion regimen. Moving forward, the authors plan dose escalation from 0.25-15 x 106 cells/kg.

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As of a data cut-off of December 31,2021, P-PSMA-101 had been administered to 14 patients with advanced mCRPC. These patients had received a median of 7 prior regimens (range 3-15). Single infusions of 0.25 (n=5) to 0.75 (n=5) x 106 cells/kg have been assessed, with dose escalation continuing.

The authors found that infusion of P-PSMA-101 cells expanded in blood via qPCR assay, peaking 2-3 weeks after infusion, consistent with the high percentage of TSCM.

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Further, in this preliminary cohort of 14 patients, significant antitumor responses were seen with declines in PSA among 10 patients, with 5 patients showing PSA declines of 50% or greater. In one patient, there was “near complete tumor elimination” with post-treatment tumor biopsy demonstrated infiltration by P-PSMA-101 CAR-T cells and elimination of tumor cells (pathologic complete response).

The authors observed a safety signal that was consistent with expectations for a CAR-T product.

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Cytokine release syndrome (CRS) was seen in 57% of patients, with a grade 3 or higher event in 2 (14%). Dose-limiting toxicity was observed in one (10%) of the patients due to macrophage activation syndrome/uveitis. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in two patients (14%). CRS marker elevations were modest (max IL-6: 642.6 pg/mL).

Dr. Slovin, therefore, concluded that these preliminary clinical data of P-PSMA-101 parallel the pre-clinical results and show promising efficacy with benefits seen in biochemical, radiographic, and pathologic parameters.

Presented by: Susan F. Slovin MD, PhD, FACP, Memorial Sloan Kettering Cancer Center, New York, NY