177Lu-CTR-FAPI for the Treatment of Thyroid Cancer

177Lu-CTR-FAPI for the Treatment of Thyroid Cancer: A Prospective, Multi-center, Open-labeled, Single-arm, Phase I Study

This is a multi-center, open-label, single-arm, dose-escalation phase I study, aiming to evaluate the safety and efficacy of 177Lu-CTR-FAPI (covalent targeted radioligand-fibroblast activation protein inhibitor), a novel radiopharmaceutical in the treatment of thyroid cancer. The primary endpoint of the study is the safety of 177Lu-CTR-FAPI, and the secondary endpoints include treatment response and dosimetry evaluation.

Study Overview

• Status: Recruiting
• Conditions: Thyroid Cancer
• Intervention / Treatment: Drug: 177Lu-CTR-FAPI therapy

Detailed Description

This clinical trial aims to evaluate the safety, tolerability, and preliminary efficacy of 177Lu-CTR-FAPI in patients with thyroid cancer. The study is designed to characterize the safety profile and dose-limiting toxicities (DLTs) in order to determine the maximum tolerated dose (MTD) of 177Lu-CTR-FAPI. Additionally, the study will assess biochemical responses, radiological responses and improvement of life quality as well as the dosimetry profile of this molecule.

This is a multi-center, open-label, single-arm phase I trial using a classic "3+3" dose-escalation design. The starting dose is 100 mCi and increases in 50 mCi increments for subsequent cohort. The MTD is defined as the highest dose at which fewer than 33% of participants experience a DLT during the 6-week observation period following the first administration. A total of 12 eligible participants with thyroid cancer will be enrolled and receive intravenous infusions of 177Lu-CTR-FAPI every 6 weeks, for up to 4 cycles. Dose delays are permitted based on evaluation of treatment response or the necessity for recovery from adverse reactions, with a maximum delay of 12 weeks after the previous dose.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ziren Kong, M.D.; Phone Number: 0086-18500487274; Email: zrkong@126.com

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Xin Zhang, M.D.; Phone Number: 0086-010-69154713; Email: zhangxin37@pumch.cn
  • Beijing, China, 100021
    • Recruiting
    • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Contact: Ziren Kong, M.D.; Phone Number: 0086-18500487274; Email: zrkong@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of thyroid cancer according to the 2022 WHO classification of thyroid tumors. Differentiated thyroid carcinoma must be diagnosed as radioactive iodine-refractory (RAIR) by a nuclear medicine specialist.
• Evidence of progressive disease based on RECIST 1.1 criteria in pre-treatment imaging.
• Prior surgical resection of resectable cervical lesions, with currently unresectable systemic disease.
• Previous targeted therapy was discontinued due to intolerance, or lack of benefit from targeted therapy assessed by investigator, or patient refusal.
• At least one measurable target metastatic lesion on contrast-enhanced CT/MRI (longest diameter of lesion ≥ 10 mm or shortest diameter of lymph node ≥ 15 mm).
• Positive CTR-FAPI uptake in lesions, defined as SUVmax > 10 in more than half of the lesions on 68Ga-CTR-FAPI PET/CT.
• Life expectancy > 6 months.
• ECOG performance status ≤ 2.
• Prior anti-tumor therapy-related toxicities that recoverd to Grade 0 or 1 (except alopecia, pigmentation, or chronic radiation toxicities and deemed irreversible by the investigator).
• For subjects with fertility: agreement to use effective contraception during treatment and 4 months (males) or 7 months (females) after the last dose.
• Voluntary participation and signed informed consent.

Exclusion Criteria:

• Presence of CTR-FAPI-negative lesions (i.e., malignant lesions on contrast-enhanced CT/MRI without uptake on 68Ga-CTR-FAPI PET/CT).
• Prior therapeutic radionuclide therapy (except 131I).
• Systemic anti-cancer therapy (including chemotherapy, targeted therapy, immunotherapy, radionuclide therapy, or anti-tumor traditional Chinese medicine) within 4 weeks before the first dose.
• Participation in another drug or device clinical trial within 4 weeks before the first dose.
• Insufficient major organ function.
• Severe or uncontrolled comorbidities.
• Presence of pleural effusion or ascites requiring intervention or judged uncontrolled by the investigator at screening.
• Active infection within 4 weeks before the first dose.
• Women who are pregnant, breastfeeding, or planning pregnancy.
• Known allergy to contrast agents.
• History of symptomatic central nervous system metastases.
• Other concurrent malignancies.
• Surgery under general anesthesia within 8 weeks before the first dose.
• History of acute coronary syndrome or stroke within 8 weeks before the first dose.
• Severe claustrophobia.
• Any other condition deemed inappropriate for participation by the investigator (e.g., poor compliance, inability to cooperate with treatment and follow-up).

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: 177Lu-CTR-FAPI Arm; Participants will receive intravenous infusions of 177Lu-CTR-FAPI every 6 weeks for up to 4 cycles. A standard "3+3" dose-escalation design will be utilized, with starting dose of 100mCi and subsequent dose levels increasing by 50 mCi increments. Dose delays are permitted based on the recovery from adverse reactions and treatment response.

Drug: 177Lu-CTR-FAPI therapy; 177Lu-CTR-FAPI will be diluted in 100 mL of normal saline and administered via slow intravenous infusion over 20-30 minutes. Dose will be escalated according to a "3+3" design, starting at 100 mCi and increasing in 50 mCi increments for subsequent cohort. Vital signs will be measured before and after drug administration. Throughout the infusion period, subjects will be closely monitored for any associated symptoms and adverse reactions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events, frequency of dose-limiting toxicities and maximum tolerated dose of 177Lu-CTR-FAPI in patients with thyroid cancer.	Incidence and severity of adverse events, frequency of dose-limiting toxicities(DLTs) will be evaluated within the 6-week observation period following the first administration of 177Lu-CTR-FAPI. DLTs will be assesse based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The Maximum Tolerated Dose (MTD) will be defined as the highest dose at which fewer than 33% of participants experience a DLT during the 6-week observation period following the first administration.	From enrollment to 6 weeks after the first injection of 177Lu-CTR-FAPI.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical response rate	Biochemical response of participants is deifined by the change of serum tumor markers (thyroglobulin for differentiated thyroid carcinoma and calcitonin for medullary thyroid carcinoma) from baseline as follows: Progressive disease (PD) is defined as more than 50% increase of serum tumor markers; Stable disease (SD) is defined as less than 50% increase or 50% reduction of serum tumor markers; Partial response (PR) is defined as more than 50% reduction of baseline serum tumor markers; Complete response (CR) is defined as normalization of serum tumor markers. The overall response rate (ORR) is measured as the proportion of participants achieving biochemical CR or PR, and the disease control rate (DCR) is defined as the proportion of participants achieving biochemical CR, PR, or SD.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
Duration of biochemical response	Duration of biochemical response is measured as the time period during which participants achieving biochemical CR or PR.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
Radiological response rate	The radiological response is evaluated by radiological examinations, including contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. The ORR is measured as the proportion of participants achieving CR or PR, and the DCR is defined as the proportion of participants achieving CR, PR, or SD.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
Duration of radiological response	Duration of radiological response is measured as the time period during which participants achieving radiological CR or PR.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
Progression-free survival	Progression-free survival (PFS) is defined as the time from enrollment until the first occurrence of disease progression or death from any cause, whichever occurs earlier.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
Overall survival	Overall survival (OS) is defined as the time from enrollment until death from any cause.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
Change of quality of life score	Change of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) scores compared with baseline is measured to evaluate improvement of life quality, in which a higher score of Function Scales and Global Health Status / Quality of Life Scale (transformed range 0-100) indicates better functioning or a higher quality of life and a lower score of Symptom Scales (transformed range 0-100) indicates less severity or frequency of the symptom.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
Change of Pain score	Change of Brief Pain Inventory (BPI) scores compared with baseline is measured to evaluate pain severity (range 0-10) and pain interference (range 0-10), and a lower score indicates a better outcome.	From enrollment to 1 year after the last 177Lu-CTR-FAPI injection.
The absorbed doses for major organs and tumors of 177Lu-CTR-FAPI	After the first administration, participants will undergo radiation dosimetry assessments. Blood samples will be collected at specific time points for radioactivity measurements. Whole-body planar imaging as well as regional quantitative single photon emission computed tomography/computed tomography (SPECT/CT) at specific time points will also be performed. Regions of interest (ROI) will be delineated on SPECT images for lesions, kidneys, bone marrow, total skeleton, heart, liver, and spleen. These ROIs will be projected onto the whole-body images to derive time-activity curves and residence times. The OLINDA software will then be used to calculate the absorbed radiation doses in tumors and normal organs.	From enrollment to 8 days after the first administration
The maximum dose	The maximum dose will be acquired based on the organ dose limits calculated from the radiation dosimetry assessments.	From enrollment to 8 days after the first administration

Collaborators and Investigators

• Sponsor: SHAOYAN LIU
• Collaborators: Peking Union Medical College Hospital; Navy General Hospital, Beijing; Beijing Tsinghua Changgeng Hospital
• Investigators: Principal Investigator: Yansong Lin, M.D., Peking Union Medical College Hospital; Principal Investigator: Shaoyan Liu, M.D., Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Publications and helpful links

General Publications

• Kong Z, Li Z, Cui XY, Wang J, Xu M, Liu Y, Chen J, Ni S, Zhang Z, Fan X, Huang J, Lin Y, Sun Y, He Y, Lin X, Meng T, Li H, Song Y, Peng B, An C, Gao C, Li N, Liu C, Zhu Y, Yang Z, Liu Z, Liu S. CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma. Cancer Discov. 2025 Feb 7;15(2):316-328. doi: 10.1158/2159-8290.CD-24-0897.
• Cui XY, Li Z, Kong Z, Liu Y, Meng H, Wen Z, Wang C, Chen J, Xu M, Li Y, Gao J, Zhu W, Hao Z, Huo L, Liu S, Yang Z, Liu Z. Covalent targeted radioligands potentiate radionuclide therapy. Nature. 2024 Jun;630(8015):206-213. doi: 10.1038/s41586-024-07461-6. Epub 2024 May 22.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: February 23, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Radionuclide therapy; Thyroid cancer; CTR-FAPI
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: BRP-010-003

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