Alpha Fusion Inc. has announced the commencement of a Phase I clinical trial for its alpha-emitting radiopharmaceutical, af-001, aimed at patients with differentiated thyroid cancer. This announcement was made on October 31, 2025, in Tokyo. The trial, identified as jRCT2031250472, specifically targets patients with papillary and follicular carcinoma who have not previously received radioactive iodine (RAI) therapy.
The design of this clinical trial builds upon findings from an investigator-initiated Phase I study conducted at the University of Osaka. It comprises two parts: Part Ia and Part Ib. In Part Ia, researchers will establish the maximum tolerated dose (MTD) for a single intravenous administration of af-001 among patients who are refractory to or intolerant of standard treatments. Part Ib will focus on assessing the efficacy and safety of multiple administrations of af-001 to determine the appropriate dosage for subsequent Phase II trials.
Part Ia of the study will take place at the National Cancer Center Hospital East, led by Principal Investigator Dr. Makoto Tahara, who heads the Department of Head and Neck Medical Oncology. In contrast, Part Ib will be conducted across multiple sites throughout Japan. The overarching goal of the clinical development of af-001 is to secure regulatory approval for its use in RAI-naïve patients suffering from differentiated thyroid cancer.
If the trial demonstrates clinical efficacy and safety, af-001 is anticipated to serve as a next-generation radiopharmaceutical and provide a novel treatment avenue for patients with differentiated thyroid cancer. The manufacturing of af-001 is performed under Good Manufacturing Practice (GMP) guidelines in collaboration with the Kobe City Medical Center General Hospital, ensuring timely delivery to the National Cancer Center Hospital East post-production.
Sunao Fujioka, CEO of Alpha Fusion, expressed optimism regarding the trial”s initiation, stating, “Based on the achievements of the investigator-initiated Phase I study in patients refractory or intolerant to standard therapies, we expect to maximize the potential of af-001 by confirming its safety and efficacy in RAI-naïve patients. Alpha Fusion is fully committed to advancing the clinical development of af-001, with the ultimate goal of providing outpatient alpha-emitting radiopharmaceutical therapy to more patients with thyroid cancer.” He also noted ongoing efforts to explore various research and development pipelines utilizing astatine-211, aiming to innovate radiopharmaceuticals for diverse cancer types.
RAI therapy is currently the standard treatment for differentiated thyroid cancer; however, it may necessitate multiple treatments in cases of extensive metastasis or inadequate response despite clear iodine uptake. Due to radiation protection regulations in Japan, RAI therapy requires administration in shielded environments, often leading to hospitalization. This situation can impose psychological stress on patients and financial burdens on healthcare facilities. A survey revealed an average waiting period of approximately 3.7 months for RAI therapy, with a significant percentage of facilities reporting wait times exceeding six months.
Given these challenges, there is an increasing demand for patient-centric radiopharmaceuticals capable of delivering effective tumor-reducing outcomes in an outpatient context.
af-001, the investigational drug in question, contains astatine-211 as its active ingredient. It is specifically absorbed by differentiated thyroid cancer cells via the sodium/iodide symporter (NIS) and delivers cytotoxic effects through the emission of alpha particles. These alpha particles have a higher energy output compared to beta particles, resulting in double-strand DNA breaks within cancer cell nuclei and facilitating tumor regression. Because the range of alpha particles is limited to several tens of micrometers, af-001 can provide significant therapeutic benefits while reducing damage to adjacent healthy tissue, potentially allowing for outpatient treatment.
Before this company-sponsored trial, a separate investigator-initiated Phase I clinical trial, known as the Alpha-T1 Trial, was conducted at the University of Osaka. This trial, which also involved NaAt, demonstrated promising safety and tolerability profiles in patients with differentiated thyroid cancer who were resistant or intolerant to conventional therapies. Notably, the trial reported reductions in thyroglobulin levels, a crucial tumor marker, alongside the disappearance of 131I uptake on imaging studies.
The current company-sponsored trial aims to establish the efficacy and safety of af-001 in RAI-naïve patients, focusing on determining the recommended dose for upcoming Phase II studies.
Alpha Fusion Inc. is committed to advancing the field of oncology through innovative radiopharmaceutical therapies that utilize radioactive isotopes. The company collaborates with various domestic and international medical and research institutions to develop new treatment options and further the evolution of precision radiopharmaceutical medicine.
For more information, please visit Alpha Fusion”s official website.
