AdvanCell Initiates Phase 2 Expansion Trial of ADVC001, a Novel Targeted Alpha Therapy for Prostate Cancer

Clinical development of 212Pb-ADVC001 (ADVC001) is advancing rapidly with encouraging Phase 1b data presented at ESMO 2025 The Phase 2 expansion will evaluate 160 MBq and 200 MBq doses of ADVC001 using a randomized, multi-dose-response design and adaptive dosing strategies to optimize clinical outcomes across three indications: metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) in pre-chemotherapy and post-177Lu-PSMA radioligand therapy (RLT) settings

AdvanCell, a clinical-stage radiopharmaceutical company developing innovative targeted alpha therapies for cancer, today announced the initiation of the TheraPb Phase 2 expansion trial (NCT05720130) evaluating its lead investigational candidate, ADVC001, in metastatic prostate cancer. The news follows the encouraging Phase 1b dose escalation results presented at the European Society for Medical Oncology (ESMO) 2025 congress that showed a favorable safety profile and compelling anti-tumor activity for ADVC001 in patients with mCRPC (see press release).

ADVC001 is a first-in-class 212Pb-PSMA RLT in clinical development, with early data indicating a differentiated and competitive profile both within and beyond its class. Development is advancing rapidly; the Phase 1b therapeutic cohorts were enrolled within ten months, and the commencement of Phase 2 expansion sustains this strong program momentum.

The TheraPb Phase 2 expansion will evaluate ADVC001 at two therapeutic dose levels – 160 MBq and 200 MBq – using a randomized, multi-dose-response design aligned with the US Food and Drug Administration (FDA) guidance on dose optimization for oncology therapeutic radiopharmaceuticals¹. The study will incorporate novel dosing strategies and the option for treatment with more than six cycles, supported by the favorable dosimetry and pharmacokinetics data from Phase 1b, to optimize clinical outcomes across three key prostate cancer indications:

• mHSPC: patients with metastatic hormone-sensitive prostate cancer
• mCRPC, pre-chemotherapy: patients with mCRPC who have not received prior chemotherapy for mCRPC
• mCRPC, post-177Lu-PSMA RLT: patients with mCRPC who have been previously treated with 177Lu-PSMA

Enrollment for the TheraPb Phase 2 expansion is expected to commence initially at clinical sites in Australia, with planned expansion to sites in the United States in 2026.

“We are excited to initiate the Phase 2 expansion, marking an important milestone in advancing our novel alpha therapy for prostate cancer,” said Anna Karmann, MD PhD, Chief Medical Officerat AdvanCell. “Our Phase 1 results enable us to evaluate optimal dosing regimens that support a precision treatment strategy aligned with tumor biology and individual response, underscoring our commitment to deliver better clinical outcomes and quality of life for patients living with metastatic prostate cancer.”

“As ADVC001 enters Phase 2, I am eager to begin enrollment in this study,” said Aaron Hansen, MD, Principal Investigator at the Princess Alexandra Hospital. “ADVC001 has demonstrated a highly promising safety and efficacy profile in Phase 1, supporting its investigation in multiple settings. The adaptive dosing and the ability to treat with more than six cycles offer the potential to meaningfully improve clinical benefit and are a step towards more personalized treatment for patients with prostate cancer.”

AdvanCell plans to present additional details on the TheraPb Phase 2 expansion trial design at a major oncology conference in the first half of 2026.

¹US Food and Drug Administration (2025, August) “Oncology Therapeutic Radiopharmaceuticals: Dosage Optimization During Clinical Development – Guidance for Industry (Draft Guidance)”

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About 212Pb-ADVC001

212Pb-ADVC001 (ADVC001) is a proprietary and patented PSMA-targeting radioligand with optimized physicochemical properties labelled with 212Pb, an alpha-emitting payload (radionuclide) with a high dose rate, 10.6 hours half-life and simple decay scheme. ADVC001 is designed to deliver radiation at a cellular level to effectively kill prostate cancer cells while minimizing toxicity.

About the TheraPb trial

The TheraPb trial (NCT05720130) is a prospective, open-label Phase 1/2 dose escalation and expansion study designed to determine the safety and tolerability of escalating doses of ADVC001 administered every 6, 4, 2 or 1 week(s) during the dose-finding Phase 1b. The Phase 2 expansion will assess the efficacy and safety of ADVC001 at the recommended Phase 2 doses across three indications. The trial utilizes a randomized dose-response design and dose optimization elements to rigorously evaluate optimal dosing strategies of ADVC001 in PSMA-positive mCRPC and in mHSPC.

About AdvanCell

AdvanCell is a vertically integrated, clinical-stage radiopharmaceutical company dedicated to developing innovative cancer therapies that harness the power of targeted alpha-emitting radionuclides. By leveraging its proprietary ²¹²Pb (Lead-212) platform, advanced and scalable manufacturing and world-class clinical development capabilities, AdvanCell aims to deliver novel treatments that improve outcomes for patients with cancer globally. For more information, visit www.advancell.com.au and follow us on LinkedIn.

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