P‑PSMA‑101 CAR‑T Therapy in Advanced Prostate Cancer: Early Results from a Phase 1 Trial

P‑PSMA‑101 is an experimental CAR‑T cell therapy being tested in men with metastatic castration‑resistant prostate cancer (mCRPC) who have already received multiple standard treatments (up to 10 before enrollment). In the phase 1 trial, 33 men with heavily pretreated mCRPC received P‑PSMA‑101, an autologous PSMA‑targeted CAR‑T product enriched in stem‑cell‑like memory T cells and engineered using a non‑viral transposon system plus a safety “off‑switch” (iCasp9).

The treatment was associated with clinically meaningful toxicity: 18% of patients experienced a dose‑limiting toxicity, 61% had cytokine release syndrome (9% grade ≥3), and 24% required activation of the iCasp9 safety switch to reduce CAR‑T burden; one treatment‑related death was reported. Despite this, the therapy produced measurable antitumor activity: 21% of patients had a ≥50% PSA decline, with one patient showing a PSA drop >99%. Among 13 RECIST‑evaluable patients, 1 had a partial radiographic response, and several patients had improved or resolved lesions on PSMA‑PET and other imaging.

Stable disease was seen in 61% of patients, with 21% maintaining stable disease for at least 3 months and 2 patients having remissions lasting more than 12 months. The product expanded in the blood over 2–3 weeks and showed evidence of bone‑tropic behavior, consistent with its design to target bone‑metastatic disease. Overall, P‑PSMA‑101 demonstrates that PSMA‑directed CAR‑T cells can induce PSA and imaging responses and disease stabilization in a subset of heavily pretreated mCRPC patients.

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