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