First in-human investigator-initiated clinical trial started for refractory thyroid cancer patients: Novel targeted alpha therapy using astatine

A research team from the Graduate School of Medicine at Osaka University has started an investigator-initiated clinical trial of sodium astatine ([²¹¹At]NaAt) injection for refractory differentiated thyroid cancer patients. The phase I trial evaluates the safety, pharmacokinetics, and efficacy of astatine for use in alpha therapy in patients with refractory differentiated thyroid cancer who responded inadequately to standard of care.

Most thyroid cancers are differentiated cancer and take up iodine like normal thyroid cells. Radioactive iodine (¹³¹I) has long been used clinically for patients with differentiated thyroid cancer in isolated hospital rooms dedicated to radionuclide treatment. However, some patients with multiple metastases are refractory to repetitive ¹³¹I treatment despite the targeted regions showing sufficient iodine uptake, and medical institutions have difficulty in maintaining dedicated wards due to limited funds and human resources.

In addition, as radioactive iodine (¹³¹I) also emits gamma rays which have a long range, patients need to be admitted alone to special hospital rooms to protect others from radiation exposure. With an increasing number of elderly patients who require help by caregivers, there has been a need for treatment that can be safely implemented on an outpatient basis.

Astatine (²¹¹At) is a halogen element with similar chemical properties to iodine. Alpha particles emitted from ²¹¹At have higher linear energy transfer as compared to beta particles from ¹³¹I, exerting a better therapeutic effect by inducing DNA double strand breaks and free radical formation. Since alpha rays are short in distance and do not travel outside the body, alpha-emitting radionuclides have been approved for outpatient cancer treatment.

“We have demonstrated the efficacy and safety of sodium astatine ([²¹¹At]NaAt) injection (trial ingredient code: TAH-1005) in preclinical studies and achieved its stable in-hospital production as an investigational drug at Osaka University Hospital,” says Tadashi Watabe, the investigator of the study.

After approval by the hospital’s institutional review board and regulatory authority, TAH-1005 will be administered to humans for the first time in the world. In the clinical trial, therapy is initiated with a low dose, then doses are titrated upwards. The trial period is between Nov. 2021 and Mar. 2024 with a maximum sample size of 16.

“Once astatine injection is approved as a pharmaceutical product, we expect that alpha therapy will be conducted in an outpatient setting. Single outpatient injection will yield a high therapeutic effect with less burden on both patients and medical institutions,” Watabe notes. “Also, astatine can be labeled with various molecules and antibodies and has the potential to be used as a therapeutic agent for various types of cancer in the future.”