ADVC001: Lead-212 PSMA Alpha Therapy Shows Safety and Efficacy in mCRPC Trial

At the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, new clinical data from a Phase 1b dose escalation trial investigating ADVC001, a novel Lead-212-based PSMA-targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) was presented. The therapy utilizes a radioactive isotope, Lead-212, to deliver targeted alpha radiation to prostate cancer cells, aiming to maximize tumor cell kill while minimizing toxicity to normal tissues.

The trial explored escalating doses administered at intervals ranging from six weeks to one week over multiple cycles. The study reported a favorable safety profile, with no dose-limiting toxicities or treatment-related serious adverse events. The most common side effect was mild, reversible dry mouth (xerostomia).

Efficacy signals in the trial were promising. About 80% of patients receiving doses at or above 160 MBq experienced at least a 50% reduction in prostate-specific antigen (PSA), an important biomarker of prostate cancer activity. Additionally, all patients with measurable tumors demonstrated objective responses, including two complete responses. These responses appeared within weeks of starting treatment.

The pharmacokinetic and dosimetry data supported the potential for administering multiple treatment cycles with sustained therapeutic impact while respecting safety. Following these encouraging Phase 1b results, the next phase of the trial will investigate optimized dosing schedules in a randomized setting across different prostate cancer populations, including chemotherapy-naïve mCRPC, those previously treated with lutetium-177 PSMA therapy, and metastatic hormone-sensitive prostate cancer.

These findings represent the first clinical data for a Lead-212 PSMA-targeted alpha therapy and may provide a new therapeutic approach for metastatic prostate cancer that balances efficacy and tolerability.

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