Metastatic Solid Tumors (Any Localization)
Conditions
Brief summary
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.
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.
Interventions
DRUGradionuclide therapy with [177Lu]Lu--TEFAPI-06
A Novel Albumin-Binding FAPI Radiopharmaceutical for Theranostics
Sponsors
Lanzhou University Second Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 | From Baseline up to 30 days after the last dose of study intervention (approximately 4 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in [18F]-FAPI PET/CT Parameters in Target Lesions | Baseline (Day 0) and 1 month post-treatment. | \[18F\]-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. |
| Change from Baseline in Tumor-Specific Serum Marker Levels | Baseline (Day 0) and 1 month post-treatment. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biodistribution and Pharmacokinetics of [177Lu]Lu-TEFAPI-06 | 0.5, 2, 24, 48, 72, and 120 hours post-injection. | 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) . |
| Radiation Absorbed Doses in Normal Organs and Tumor Lesions | Post-injection at 0.5, 2, 24, 48, 72, and 120 hours. | 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. |
Countries
China
Outcome results
None listed