AdvanCell Launches Pivotal Phase 2 Expansion Trial of ADVC001, a First-in-Class Targeted Alpha Therapy for Metastatic Prostate Cancer
AdvanCell, a clinical-stage radiopharmaceutical company at the forefront of developing next-generation targeted alpha therapies (TATs) for oncology, has announced the initiation of the TheraPb Phase 2 expansion trial (NCT05720130) for its lead investigational agent, ADVC001. This milestone follows compelling Phase 1b data presented at the European Society for Medical Oncology (ESMO) 2025 congress, which highlighted a favorable safety profile and robust anti-tumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC).
ADVC001 is a novel ²¹²Pb-labeled prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT)—the first of its kind to enter clinical development in this class. Early clinical results suggest that ADVC001 possesses a differentiated therapeutic profile, offering potential advantages not only over existing beta-emitting radiopharmaceuticals like ¹⁷⁷Lu-PSMA but also within the emerging landscape of alpha-emitting agents. The rapid pace of development is underscored by the fact that Phase 1b therapeutic cohorts were fully enrolled in just ten months, paving the way for this critical Phase 2 expansion.
The TheraPb Phase 2 trial is designed to evaluate two fixed dose levels—160 MBq and 200 MBq—of ADVC001 in a randomized, multi-dose-response format. This design aligns with the U.S. Food and Drug Administration’s (FDA) latest guidance on dose optimization for oncology radiopharmaceuticals, emphasizing the importance of identifying the dose that maximizes efficacy while maintaining an acceptable safety margin. Importantly, the trial incorporates adaptive dosing strategies and allows for treatment beyond the conventional six-cycle limit, based on encouraging dosimetry and pharmacokinetic data from Phase 1b that demonstrated favorable biodistribution and manageable radiation exposure to healthy tissues.
The study will assess ADVC001 across three clinically relevant and distinct prostate cancer populations:
- Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Patients who remain responsive to androgen deprivation therapy but have widespread disease.
- Metastatic Castration-Resistant Prostate Cancer (mCRPC), Pre-Chemotherapy: Patients whose disease has progressed despite hormonal therapy but who have not yet received chemotherapy.
- mCRPC, Post-¹⁷⁷Lu-PSMA RLT: Patients whose cancer has progressed following treatment with lutetium-177 PSMA therapy—a rapidly growing population in need of effective next-line options.
This broad indication strategy reflects AdvanCell’s ambition to position ADVC001 as a versatile therapeutic option across the metastatic prostate cancer continuum, addressing unmet needs at multiple stages of the disease.
Initial patient enrollment for the TheraPb trial is set to begin at clinical sites in Australia, with expansion into U.S. centers planned for 2026. The global trial design aims to accelerate recruitment and generate robust, diverse clinical data to support future regulatory submissions.
Dr. Anna Karmann, Chief Medical Officer at AdvanCell, emphasized the significance of this next phase: “We are thrilled to advance ADVC001 into Phase 2. Our Phase 1 results not only confirmed its safety but also revealed promising signs of clinical activity, giving us confidence to explore optimized dosing regimens. Our goal is to deliver a precision medicine approach—tailoring therapy based on tumor biology and individual patient response—to improve both outcomes and quality of life for men battling advanced prostate cancer.”
Dr. Aaron Hansen, Principal Investigator at Princess Alexandra Hospital and a leading expert in nuclear medicine oncology, echoed this optimism: “ADVC001’s early data are highly encouraging. The ability to administer more than six treatment cycles, combined with adaptive dosing, opens new possibilities for personalizing care. This trial represents a significant step toward redefining the standard of care in metastatic prostate cancer.”
AdvanCell intends to present comprehensive details of the TheraPb Phase 2 trial design—including endpoints, biomarker strategy, and statistical framework—at a major oncology conference in the first half of 2026. With strong preclinical rationale, compelling early clinical data, and a well-structured development pathway, ADVC001 is poised to become a potential cornerstone in the evolving treatment paradigm for prostate cancer.
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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