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

First-in-Human Safety and Dosimetry Study of ¹⁷⁷Lu-FAPI in Patients With FAP-Positive Malignancies

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Patients With Advanced Metastatic FAP-Positive Tumors
• Intervention / Treatment: Drug: 177Lu-JH040182 with an activity of approximately 5.55-7.50 GBq

Detailed Description

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
• Enrollment (Estimated): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University

Participation Criteria

Eligibility Criteria

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

Description

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

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: Intravenous administration of 177Lu-JH040182; It is planned to recruit 3 subjects with FAP-positive tumors for administration of 177Lu-JH040182 at a dose ranging from 5.55 to 7.50 GBq.	Drug: 177Lu-JH040182 with an activity of approximately 5.55-7.50 GBq; Subjects will receive intravenous administration of 177Lu-JH040182 at an activity of approximately 5.55-7.50 GBq.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment till 30 days safety follow-up, assessed up to 50 months (estimated final OS analysis)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	through study completion, an average of 4 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Fujian Medical University
• Investigators: Principal Investigator: Weibing Miao, MD, The First Affiliated Hospital, Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: fibroblast activation protein; lutetium-177
• Other Study ID Numbers: FirstAHFujian-177Lu-JH040182

Drug and device information, study documents

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