Australian biotechnology company AdvanCell has unveiled the first clinical results of its novel targeted alpha therapy 212Pb-ADVC001 for prostate cancer at the European Society for Medical Oncology Congress 2025, marking a significant moment in the evolution of PSMA-targeted radioligand therapy.
The findings from the Phase 1b dose-escalation of the TheraPb clinical trial (NCT05720130) show a favourable safety profile and strong early signs of efficacy in men with metastatic castration-resistant prostate cancer (mCRPC).
“We are very encouraged by the completion of the treatment period of our Phase 1 trial, which has demonstrated a favourable safety profile and compelling anti-tumour activity for 212Pb-ADVC001,” said Anna Karmann, Chief Medical Officer at AdvanCell. “These results underscore the potential of our therapy to meaningfully impact patients’ lives and advance treatment options in metastatic prostate cancer. I want to sincerely thank the investigators, clinical teams, and most importantly the patients and their families, whose commitment has made this important milestone possible.”
The data presented represent the first clinical trial results of a Lead-212 targeted alpha therapy in prostate cancer. The therapy is designed to selectively target PSMA-expressing tumours and deliver potent alpha radiation while sparing normal tissue.
According to Aaron Hansen, Principal Investigator at Princess Alexandra Hospital, the results mark “a pivotal step forward” for the field. “We’ve observed a compelling therapeutic index, including marked reductions in tumour volume and PSA, alongside a promising safety and dosimetry profile,” he said. “The ability to administer alpha therapy easily and efficiently in an outpatient setting is a major clinical advantage. I am excited about the potential of 212Pb-ADVC001 to redefine treatment for patients with prostate cancer.”
The Phase 1b study enrolled 22 patients with mCRPC. Participants received escalating doses of 60–200 MBq of 212Pb-ADVC001 at intervals ranging from six weeks to one week for up to six cycles. The data, with a cut-off of October 2, 2025, showed no dose-limiting toxicities, no treatment-related serious adverse events, and no treatment discontinuations. Xerostomia, the most common side effect, was predominantly mild and reversible. At therapeutic doses of 160 MBq or higher, 80 per cent of patients experienced a PSA50 biochemical response, and every patient with measurable disease had an objective response, including two complete responses. PSA, imaging and clinical responses were often seen within weeks of treatment initiation. Dosimetry data indicated low normal-organ exposure, rapid clearance and no significant metabolic breakdown.
“This is an extremely promising step forward in delivering targeted alpha therapy to patients with prostate cancer,” said Oliver Sartor, Director of the Transformational Prostate Cancer Research Center at East Jefferson General Hospital. “The efficacy signal and safety profile are very strong.”
AdvanCell will now move into Phase 2 expansion, evaluating 160 MBq and 200 MBq doses of 212Pb-ADVC001 using a randomised multi-dose-response design and adaptive dosing strategies. The study will target chemo-naïve mCRPC, post-177Lu-PSMA mCRPC, and metastatic hormone-sensitive prostate cancer (mHSPC). Dr Karmann said the company’s ambition is to establish a new standard of care in prostate cancer. “We believe 212Pb-ADVC001 has the potential to redefine expectations for PSMA-targeted therapies,” she said.