A Phase I Trial of Af-001 in Patients With Differentiated Thyroid Cancer

A Phase I Trial of the Alpha Particle-emitting Radiopharmaceutical, Af-001, in Patients With Differentiated Thyroid Cancer

This trial consists of 2 parts, i.e., Part Ia and Ib. The Part Ia is to evaluate the safety and tolerability of a single intravenous dose of af-001 in patients with radically unresectable, recurrent, metastatic differentiated thyroid cancer (papillary carcinoma, follicular carcinoma) refractory to or intolerant of standard-of-care therapy, who have received total thyroidectomy, and to determine the MTD (Maximum tolerated dose).

Part Ib is to evaluate the efficacy and safety of af-001 mutiple doses to patients with radically unresectable, recurrent, metastatic differentiated thyroid cancer (papillary carcinoma, follicular carcinoma), who have received total thyroidectomy and are RAI naïve, randomized into two arms at the determined MTD or the MTD-1 dose level, and to determine the recommended Phase II dose (RP2D)

Study Overview

• Status: Recruiting
• Conditions: DTC - Differentiated Thyroid Cancer
• Intervention / Treatment: Drug: [211At]NaAt

Detailed Description

The Part Ia is a dose escalation part. The Part Ib is a parallel-group comparative study part based on the MTD determined in Part Ia, in which 10 patients each will be randomly assigned to one of two treatment arms, at the MTD for af-001 or the MTD-1 dose level. Patients will be randomly assigned by the enrollment system (allocated at a ratio of 1:1). Random assignment will be performed using the stratified permuted block method. The stratification factor will be the site(s) of metastases.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alpha Fusion Clinical Development; Phone Number: +81335185330; Email: development@alpha-fusion.com

Study Locations

• Japan
  • Kashiwa, Japan
    • Recruiting
    • National Cancer Center Hospital East

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

<Ia part>

• Patients with differentiated thyroid cancer (papillary carcinoma, follicular carcinoma) after total thyroidectomy.
• Patients with radically unresectable, recurrent, metastatic disease who are judged by the principal investigator or sub-investigator (hereinafter, "principal/sub-investigators") to be refractory to or intolerant of standard-of-care therapy.

<Ib part>

• Patients with radically unresectable, recurrent, metastatic disease who are RAI naive
• Patients with measurable lesions. <Ia/Ib part>
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 and stable general condition.
• Patients expected to survive for at least 6 additional months based on clinical symptoms and physical examination findings.

Exclusion Criteria:

<Ia/Ib part>

• Patients who need to preserve fertility.
• Females who are pregnant or may be pregnant, breastfeeding patients, or patients or their partners who cannot agree to appropriate contraception.
• Patients with active multiple cancers (synchronous multiple cancers and ectopic double cancers with a disease-free period of <=3 years).
• Patients with uncontrolled active infections.
• Patients who are positive for hepatitis B virus surface (HBs) antigen, hepatitis C virus (HCV) antibodies, or human immunodeficiency virus (HIV) antibodies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [211At]NaAt; Ph1a: single dose, Ph1b: mutiple dose	Drug: [211At]NaAt; MTD or MTD-1 level to be tested

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ph1a: DLT (Dose-limiting toxicity ) based on Japanese translation of the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, Japan Clinical Oncology Group (JCOG) version	DLT evaluation criteria: Grade ≥4* hematologic toxicity that persists for at least 7 days; Febrile neutropenia regardless of duration; Grade ≥3* thrombocytopenia associated with a bleeding tendency or that requires platelet transfusions; Anemia that requires red blood cell transfusions; Neutropenia associated with infection; Grade ≥3* non-hematologic toxicity that persists for at least 7 days and does not improve with symptomatic treatment, with the following exceptions:Toxicities that can be controlled to Grade ≤2* with maximum supportive herapyThose due to the progression of the primary tumor [*: Grades as defined in CTCAE v.5.0 (Japanese translation) JCOG version]	4 weeks
Ph1b: Assessment of tumor reduction effect on MRI or CT scan images	Using the "Revised version of the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 (Japanese translation of JCOG version 1.0)" as a reference.	24 weeks

Collaborators and Investigators

• Sponsor: Alpha Fusion Inc.
• Investigators: Principal Investigator: Tahara, Chief, National Cancer Center Hospital East

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: December 3, 2025
• First Posted (Estimated): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: DTC; At211; alpha particle-emitting radiopharmaceutical
• Other Study ID Numbers: af-001TH; jRCT2031250472 (Other Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No