Clinical Study of 177Lu-JH040182 in Patients With FAP-Positive Malignancies

Phase 1Active Not RecruitingNCT07681141

First Affiliated Hospital of Fujian Medical University3 enrolled

Overview

This first-in-human study aimed to assess the safety and internal radiation dosimetry of 177Lu-JH040182, a novel FAP-targeted radiopharmaceutical, in patients with FAP-positive tumors. All patients underwent screening via 68Ga-FAPI PET/CT. Those confirmed to have FAP-positive lesions on PET imaging received administration of 177Lu-JH040182, and serial-time-point SPECT images were acquired for internal radiation dosimetry calculations.

Cancer-associated fibroblasts (CAFs) constitute a critical component of the tumor microenvironment and are widely distributed in the stroma of various malignancies. Fibroblast activation protein (FAP), a specific biomarker of CAFs, is overexpressed in more than 90% of malignant tumors but exhibits limited expression in normal tissues, rendering it an ideal target for the diagnosis and treatment of multiple cancers. To date, a variety of FAP-targeted radiopharmaceuticals have been developed for radionuclide therapy, such as 177Lu-FAPI-46 and 177Lu-FAP-2286. These agents have demonstrated potent anti-tumor efficacy and a favorable toxicity profile in oncological treatment. The novel radiopharmaceutical 177Lu-JH040182 also exhibits excellent in vitro and in vivo stability. Preclinical investigations have validated its high binding affinity, favorable safety profile and outstanding tumor selectivity, enabling specific accumulation within neoplastic tissues. This study aimed to evaluate the dosimetric effects, toxicities and therapeutic efficacy of 177Lu-JH040182 in patients with advanced metastatic cancers who failed all prior therapeutic regimens without meaningful clinical improvement. Eligible patients first underwent 68Ga-FAPI PET/CT to confirm FAP-positive lesions (defined as \>50% of lesions with an SUVmax exceeding 10). Upon confirmation, patients received intravenous administration of 177Lu-JH040182 at a radioactivity dose ranging from 5.55 to 7.40 GBq. Serial SPECT imaging was subsequently performed at multiple time points for each subject, and the absorbed doses to tumor lesions and normal physiological organs were quantified using the Hermes system software.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

Conditions

Patients With Advanced Metastatic FAP-Positive Tumors

Interventions

177Lu-JH040182 with an activity of approximately 5.55-7.50 GBqDRUG

Subjects will receive intravenous administration of 177Lu-JH040182 at an activity of approximately 5.55-7.50 GBq.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * progressive advanced metastatic tumors * tumors with high FAP expression confirmed on 68Ga-FAPI PET/CT (defined as a maximum standardized uptake value ≥10 in more than 50% of tumor lesions) * an Eastern Cooperative Oncology Group performance status of 0-2 Exclusion Criteria: * pregnant or lactating women * received other radionuclide therapy in the past 6 months * received chemotherapy, radiotherapy and other anti-tumor treatments in the past 28 days

Locations (1)

Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Outcomes

Primary Outcomes

Toxic and side effect

The distribution of adverse events (AE) will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

Time frame: From enrollment till 30 days safety follow-up, assessed up to 50 months (estimated final OS analysis)

Secondary Outcomes

Dosimetry of normal organs and tumors

After the initial administration of 177Lu-JH040182, SPECT images will be acquired at multiple time points. The Hermes system will be used to calculate and record the absorbed doses of normal organs and tumors.

Time frame: through study completion, an average of 4 weeks

Data from ClinicalTrials.gov

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