Preclinical Safety Evaluation and First-in-Human Translational Study of [177Lu]Lu-TEFAPI-06

Preclinical Safety Evaluation and First-in-Human Translational Study of [177Lu]Lu-TEFAPI-06: A Novel Albumin-Binding FAPI Radiopharmaceutical for Theranostics

This study aims to systematically evaluate the safety, biodistribution, dosimetry, and preliminary therapeutic potential of [177Lu]Lu-TEFAPI-06 through an exploratory first-in-human (FIH) trial.

Study Overview

• Status: Completed
• Conditions: Metastatic Solid Tumors (Any Localization)
• Intervention / Treatment: Drug: radionuclide therapy with [177Lu]Lu--TEFAPI-06

Detailed Description

This study represents a comprehensive "bench-to-bedside" translational investigation, providing the first systematic report on the safety profile of [177Lu]Lu-TEFAPI-06-a novel albumin-binding fibroblast activation protein inhibitor (FAPI) radiopharmaceutical-and its successful transition into a FIH. The investigators preliminarily evaluated its safety, dosimetry, and therapeutic response in patients with ibroblast activation protein (FAP)-overexpressing metastatic solid tumors.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The Second Hospital & Clinical Medical School, Lanzhou University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age > 18 years
• Histologically confirmed advanced metastatic solid tumors refractory or intolerant to standard therapies
• ECOG performance status 0-2
• Life expectancy > 3 months
• At least one FAP-avid lesion confirmed by baseline [18F]-FAPI PET/CT
• Adequate organ and bone marrow function prior to the first dose

Exclusion Criteria:

• Chemotherapy, radiotherapy, or targeted therapy within 4 weeks
• Severe hepatic or renal dysfunction
• Uncontrolled active infection or severe comorbidities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Patients with advanced metastatic solid tumors	Drug: radionuclide therapy with [177Lu]Lu--TEFAPI-06; A Novel Albumin-Binding FAPI Radiopharmaceutical for Theranostics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0	Safety and tolerability will be assessed by recording the frequency, duration, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs). The assessment includes clinically significant changes in vital signs (blood pressure, heart rate, respiratory rate, temperature), physical examination findings, 12-lead Electrocardiogram (ECG) parameters, and clinical laboratory tests (including Complete Blood Count [CBC], Urinalysis, Liver Function Tests [LFTs], and Renal Function Tests). Severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.	From Baseline up to 30 days after the last dose of study intervention (approximately 4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in [18F]-FAPI PET/CT Parameters in Target Lesions	[18F]-FAPI PET/CT images will be acquired to evaluate the expression of FAP within the tumor stroma. The efficacy assessment will be based on the quantitative analysis of Standardized Uptake Values (SUVmax and SUVmean) and Tumor-to-Background Ratios (TBR) of the target lesions. Changes in tracer uptake between the baseline scan and the follow-up scan will be calculated.	Baseline (Day 0) and 1 month post-treatment.
Change from Baseline in Tumor-Specific Serum Marker Levels	Peripheral blood samples will be collected to measure the serum concentration of tumor-specific biomarkers relevant to the indication (e.g., CEA, CA19-9, PSA, or other applicable markers). The change in concentration levels will be assessed to evaluate biochemical response.	Baseline (Day 0) and 1 month post-treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biodistribution and Pharmacokinetics of [177Lu]Lu-TEFAPI-06	Biodistribution will be assessed by quantitative analysis of Whole-Body planar and SPECT/CT images. Tracer uptake in blood, normal organs (kidneys, liver, etc.), and tumor tissues will be quantified at serial time points. Parameters to be analyzed include the percentage of injected dose (%ID) and percentage of injected dose per gram (%ID/g) for each regions of Interest (ROI) .	0.5, 2, 24, 48, 72, and 120 hours post-injection.
Radiation Absorbed Doses in Normal Organs and Tumor Lesions	Radiation dosimetry will be calculated based on biodistribution data derived from serial imaging. Following the administration of [177Lu]Lu-TEFAPI-06, Whole-Body (WB) planar scintigraphy and SPECT/CT scans will be performed. ROIs will be drawn over source organs and tumor lesions to generate time-activity curves. Absorbed doses (in Gy/GBq) will be estimated using standard dosimetry software (e.g., OLINDA/EXM or IDAC) based on the MIRD scheme.	Post-injection at 0.5, 2, 24, 48, 72, and 120 hours.

Collaborators and Investigators

• Sponsor: Lanzhou University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2023
• Primary Completion (Actual): August 16, 2024
• Study Completion (Actual): August 16, 2025

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2023A-371

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