Preclinical Safety Evaluation and First-in-Human Translational Study of [177Lu]Lu-TEFAPI-06: A Novel Albumin-Binding FAPI Radiopharmaceutical for Theranostics
Phase: EARLY_PHASE1
Conditions: Metastatic Solid Tumors (Any Localization)
Sponsor: Lanzhou University Second Hospital

STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN
Study Title: An Exploratory Clinical Study Evaluating the Safety,
Biodistribution, and Therapeutic Response of [177Lu]Lu-TEFAPI-06 in
Patients with Metastatic Solid Tumors
Protocol ID: [2023A-371]
Date: [July 27, 2023]

1. STUDY SYNOPSIS
Study Phase: Exploratory (Phase 0/I)
Investigational Product:[177Lu]Lu-TEFAPI-06
Indication: fibroblast activation protein (FAP)-high expressing metastatic
solid tumors
Methodology: Open-label, single-center, single-arm study
Sample Size: 5 participants
Intervention:Single
intravenous
injection
of
approx.
20
MBq/kg
[177Lu]Lu-TEFAPI-06.
2. INTRODUCTION AND RATIONALE
FAP is highly expressed in the cancer-associated fibroblasts (CAFs) of
the tumor microenvironment in various solid tumors, making it a
promising target for radionuclide therapy. [177Lu]Lu-TEFAPI-06 is a
novel radiopharmaceutical designed to target FAP. This study is initiated
to
evaluate
its
safety
profile,
biodistribution
characteristics,
and
preliminary therapeutic potential in humans.
3. STUDY OBJECTIVES
3.1 Primary Objectives
1. To evaluate the safety and tolerability of [177Lu]Lu-TEFAPI-06 in
patients with metastatic solid tumors.
2. To determine the biodistribution and calculate the radiation absorbed
dose in normal organs and tumor lesions.

3.2 Secondary Objective
1.To
preliminarily
assess
the
therapeutic
response
of
[177Lu]Lu-TEFAPI-06 in patients with FAP-high expressing tumors.
4. STUDY DESIGN
This is a prospective, single-center, open-label, exploratory clinical trial.
5 eligible patients will receive a single dose of the investigational drug.
Patients will undergo serial whole-body imaging to assess biodistribution
and will be followed up for 1 month to assess safety and efficacy.
5. STUDY POPULATION
5.1 Inclusion Criteria
1. Diagnosed with metastatic solid tumors via pathology.
2.Confirmed high FAP expression in tumor lesions via [18F]-FAPI
PET/CT screening (Tumor uptake significantly higher than background).
3. Expected survival time＞3 months.
4. Voluntarily signed the informed consent form.
5.2 Exclusion Criteria
1. Pregnancy or lactation.
2.Severe hepatic or renal dysfunction (e.g., Creatinine > 1.5x ULN;
ALT/AST > 3x ULN).
3. Severe hematological suppression (e.g., WBC < 3.0×10⁹/L, Platelets <
75×10⁹/L).
4. Known severe allergy to the drug or its components.

5.Any other condition that the investigator deems unsuitable for
participation.
6. TREATMENT PLAN
Drug:[177Lu]Lu-TEFAPI-06
Route of Administration: Intravenous (IV) injection.
Dosage:A single dose of approximately 20 MBq/kg.
7. STUDY ASSESSMENTS AND PROCEDURES
7.1 Imaging Schedule
Following the injection of [177Lu]Lu-TEFAPI-06, whole-body planar
imaging and SPECT/CT tomography will be performed at the following
time points:0.5 hours, 2 hours, 24 hours, 48 hours, 72 hours, and 120
hours post-injection.
7.2 Efficacy Assessment (Follow-up)
Timeline:Baseline (pre-treatment) and 1 month post-treatment.
Modality:[18F]-FAPI PET/CT.
Biological Markers:Tumor-specific serum markers will be measured at
baseline and follow-up.
7.3 Safety Assessment
Vital signs and physical examination.
Laboratory tests: Complete blood count (CBC), Urinalysis, Liver function
tests (LFTs), Renal function tests.
12-lead Electrocardiogram (ECG).

Adverse Event (AE) monitoring throughout the study.
8. STATISTICAL ANALYSIS PLAN (SAP)
8.1 General Considerations
This is a small-sample exploratory study (N=5). The statistical analysis
will be primarily descriptive. No formal sample size calculation based on
power analysis was performed due to the pilot nature of the study.
8.2 Analysis Sets
Full Analysis Set (FAS):All participants who received the study drug and
have at least one post-baseline efficacy evaluation.
Safety Set (SS):All participants who received the study drug.
8.3 Biodistribution and Dosimetry Analysis
Data Processing:Regions of Interest (ROIs) will be drawn on whole-body
SPECT/CT images for source organs (heart, lung, liver, kidney, spleen,
brain) and tumor lesions.
Calculations:
1.Radioactive counts in ROIs will be converted to activity using system
calibration factors.
2. Time-Activity Curves (TACs) will be generated for each organ.
3. Cumulative activity (residence time) will be calculated by integrating
the
TACs
(using
mono-exponential
or
bi-exponential
fitting
as
appropriate).
4.Software:OLINDA/EXM software will be used to calculate the mean

absorbed dose (mGy/MBq) for organs and the effective dose (mSv/MBq)
for the whole body.
Statistical Output:Mean and Standard Deviation (SD) of absorbed doses
per organ will be reported.
8.4 Efficacy Analysis
Primary Endpoint (Imaging):Comparison of Standardized Uptake Values
(SUVmax and SUVmean) of the primary tumor and representative
metastatic
lesions
between
baseline
and
1-month
post-treatment
[18F]-FAPI PET/CT scans.
Background Reference: Mean SUV of normal liver tissue.
Secondary Endpoint (Biomarkers):Comparison of serum tumor marker
levels pre- and post-treatment.
Statistical Test:Continuous variables (SUV, biomarker levels) will be
tested for significant changes using the Paired t-test (if normally
distributed) or Wilcoxon signed-rank test (if non-normally distributed).
A P-value < 0.05 will be considered statistically significant.
Data will be presented as Mean ± SD or Median (Range).
8.5 Safety Analysis
Adverse Events (AEs):All AEs will be coded and graded according to
CTCAE v5.0(Common Terminology Criteria for Adverse Events).
Tabulation:The number and percentage of patients experiencing AEs will
be summarized by system organ class and severity grade.

Laboratory Data:Descriptive statistics will be used to summarize changes
in hematology and chemistry values from baseline to post-treatment.
Particular attention will be given to renal toxicity and myelosuppression
(Grade 3/4 toxicity).
8.6 Handling of Missing Data
Given the small sample size, missing data will not be imputed. Analyses
will be performed on observed data only.
9. ADVERSE EVENT REPORTING
The investigator is responsible for monitoring the safety of patients. Any
Serious Adverse Event (SAE) must be reported to the Ethics Committee
within 24 hours of awareness.
10. ETHICAL CONSIDERATIONS
The study will be conducted in accordance with the Declaration of
Helsinki and Good Clinical Practice (GCP) guidelines. The protocol and
informed consent form (ICF) have been reviewed and approved by the
Institutional Ethics Committee.