Exploratory Clinical Study of ¹⁷⁷Lu-CTR-FAPI in Patients With Metastatic Solid Tumors

An Exploratory Clinical Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of ¹⁷⁷Lu-CTR-FAPI in Patients With Metastatic Solid Tumors

This is a single-center, non-randomized, single-arm, open-label exploratory clinical study of ¹⁷⁷Lu-CTR-FAPI in patients with FAP-high expressing metastatic solid tumors, with a focus on breast cancer, sarcoma, and thyroid cancer.

The purpose of this study is to evaluate the safety and tolerability of ¹⁷⁷Lu-CTR-FAPI. The study will also assess its in vivo biodistribution, radiation absorbed dose in normal organs and target lesions, and preliminary clinical efficacy.

The main question this study aims to answer is whether ¹⁷⁷Lu-CTR-FAPI can be administered safely and shows sufficient tumor-targeting and preliminary therapeutic activity to support further clinical investigation in patients with FAP-high expressing metastatic solid tumors.

This is an investigator-initiated, single-center, non-randomized, single-arm, open-label exploratory clinical trial of ¹⁷⁷Lu-CTR-FAPI in patients with FAP-high expressing metastatic solid tumors.

Participants will receive ¹⁷⁷Lu-CTR-FAPI by intravenous infusion. The planned standard activity is 200 mCi (7.4 GBq) ±10%, administered every 6±1 weeks for up to 4 cycles. Dose reduction to 100 mCi (3.7 GBq) may be performed according to predefined toxicity criteria.

During the first treatment cycle, participants will undergo intensive blood sampling and serial imaging to evaluate biodistribution and radiation dosimetry. Whole-body planar imaging and localized quantitative SPECT/CT will be performed at multiple time points from approximately 1 hour to 7-9 days after the initial administration. Regions of interest will be drawn for source organs and target lesions, and time-activity curves will be generated to estimate cumulative activity. Absorbed doses to normal organs and tumor lesions will be calculated using OLINDA/EXM software.

Safety will be monitored throughout the study by vital signs, physical examinations, laboratory tests, 12-lead electrocardiograms, and adverse event recording. Adverse events will be coded and graded according to CTCAE v5.0, with particular attention to hematologic, hepatic, and renal toxicities.

Tumor imaging evaluations will be performed according to the study schedule. Preliminary efficacy will be assessed using RECIST 1.1, including objective response rate and progression-free survival. Statistical analyses will be descriptive, and missing data will not be imputed.

Inclusion Criteria:

• Pathological diagnosis confirmed metastatic solid tumors (breast cancer, sarcoma, and some thyroid cancers, etc.) that failed standard treatment or lacked standard treatment
• Age: 75 ≥ age ≥ 18 years
• ECOG score: 0 - 2
• 68Ga-CTR-FAPI PET/CT confirmed high expression of FAP in the tumor (more than 50% of the lesions with SUVmax ≥ 10)
• The FAP immunohistochemical score of tumor cells is ≥ 2 (except for thyroid cancer)
• There is at least one measurable lesion (RECIST 1.1)
• Organ/marrow functions meet the specified thresholds, and there are no severe electrocardiogram abnormalities (QTcF ≤ 470ms)

Exclusion Criteria:

• There is brain metastasis or other central nervous system lesions.
• The expected survival period is less than 6 months.
• Within 4 weeks before administration, the patient has received chemotherapy, targeted therapy, immunotherapy, or other anti-tumor treatments or investigational drugs.
• The patient has previously received other systemic radionuclide therapy (excluding 131I treatment for thyroid cancer).
• There is uncontrolled pleural effusion, ascites, severe cardiovascular or cerebrovascular diseases, or infection.