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.

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.

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).