Bayer Begins Phase I Trial of Actinium-225 Radiopharmaceutical for Advanced Hepatocellular Carcinoma

WHIPPANY, NJ, USA I April 29, 2025 I Bayer has announced the launch of a Phase I clinical study for 225Ac-GPC3 (BAY 3547926), an innovative targeted alpha radiopharmaceutical designed to combat tumors that express Glypican-3 (GPC3) in patients suffering from advanced hepatocellular carcinoma (HCC). Glypican-3 is a protein associated with the cell membrane and is found to be overexpressed in approximately 70-75% of HCC lesions, making it a promising target for radionuclide therapies.

The first-ever human study, identified as NCT06764316, will investigate the safety, tolerability, and preliminary effectiveness of BAY 3547926 both as a standalone treatment and in combination with other therapies for patients with advanced-stage HCC. Dr. Dominik Ruettinger, Global Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division, emphasized the significance of this trial in addressing the substantial unmet needs in cancer treatment. He highlighted the potential of targeted alpha therapies, a burgeoning area in radionuclide therapy, to revolutionize precision oncology.

Liver cancer, notably hepatocellular carcinoma, ranks as the third leading cause of cancer-related mortality worldwide, with nearly 900,000 new cases diagnosed each year. In the United States, liver cancer represents the fastest-growing cause of cancer deaths, accounting for roughly 2% of new cancer diagnoses and 5% of cancer-related fatalities. Despite advances in medical research, many healthcare professionals remain dissatisfied with the therapeutic outcomes of current treatment options.

Targeted alpha therapy (TAT), an innovative class of radionuclide treatment, offers the potential to meet critical unmet medical needs across multiple cancer types. Bayer’s expanding TAT portfolio integrates alpha particle-emitting radionuclides with diverse targeting mechanisms. 225Ac-GPC3 stands as the third TAT initiative under clinical assessment and Bayer’s inaugural investigational radiopharmaceutical for HCC. It is accompanied by 225Ac-Pelgifatamab and 225Ac-PSMA-Trillium, both currently undergoing Phase I trials for patients with advanced metastatic castration-resistant prostate cancer.

On April 28, 2025, Bayer presented 225Ac-GPC3 at the American Association of Cancer Research (AACR) Annual Meeting during the “New Drugs on the Horizon” session. During this presentation, Bayer showcased the asset's preclinical characterization, which included observations of minimal uptake and rapid clearance from normal organs, as well as evidence of tumor regression in in vivo models. This recognition at such a prestigious symposium underscores Bayer's commitment to its precision oncology development portfolio.

BAY 3547926, the investigational targeted alpha radiopharmaceutical, consists of a GPC3 targeting high-affinity antibody labeled with actinium-225 (225Ac). This compound delivers potent alpha particles directly to GPC3-expressing cancer cells, potentially inducing DNA double-strand breaks and reducing cancer cell viability, which may lead to anti-tumor activity.

Targeted alpha therapy represents a promising class of radionuclide treatments that can target a wide range of tumors. By delivering alpha particle radiation directly to the tumor, TAT minimizes impact on surrounding healthy tissue. Actinium-225, with its 9.9-day half-life, is an alpha particle-emitting radionuclide that deposits highly ionizing radiation over a short distance. This precise delivery system ensures effective treatment while minimizing damage to nearby normal tissues.