Clinical Evaluation of 177Lu-DOTA-EB-FAPI in Patients With Various Solid Tumors

Study Overview
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Brief Summary
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Increased fibroblast activation protein expression is positively correlated with the aggressiveness of cancer. Radiolabeled fibroblast activation protein inhibitor therapy, also known as radioligand therapy has become a novel treatment for patients with refractory cancer and disease progression after multiple-lines treatment. However, a major problem in the therapeutic use of 177Lu-DOTA-FAPI has been its short half-life and fast rate of clearance. This study was designed to evaluate the safety and tolerabilityof a long-lasting radiolabeled fibroblast activation protein inhibitor 177Lu-DOTA-EB-FAPI in patients with various refractory solid tumors.

Detailed Description
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This IIT study will include a maximum of 20 subjects with progressive cancer after multiple-line treatment, with an increased radiotracer uptake in tumors on 68Ga-FAPI-46 PET/CT. The fixed dose of 177Lu-DOTA-EB-FAPI is 3.7GBq (100 mCi). Treatment is planned for up to 2 cycles, and the time interval between cycles is 6 weeks. The primary endpoint assessed the safety and maximum tolerated dose of 177Lu-DOTA-EB-FAPI used for radioligand therapy in patients with various advanced tumors. Secondary endpoints included dosimetry and determination of the preliminary treatment efficacy of 177Lu-DOTA-EB-FAPI.

Official Title
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An Open-Label, Non-Randomized, Single-Center, Investigator-Initiated Trial to Determine the Safety, Dosimetry, and Preliminary Effectiveness of 177Lu-DOTA-EB-FAPI in Patients With Various Solid Tumors

Conditions
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Refractory Solid Tumor

Intervention / Treatment
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* Drug: 177Lu-DOTA-EB-FAPI radionuclide therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and willingness to sign a written informed consent document. Age 18 and older. Confirmed unresectable or metastatic refractory cancer with measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion > 1 cm or lymph node > 1.5 cm in short axis). Progressive disease after multiple-lines treatment. Eastern Cooperative Oncology Group Performance Status ≤ 3. Participant must have completed prior therapy at least 2 weeks (washout period) prior to 68Ga-FAPI-46 PET/CT scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved below Grade 2 or baseline. Completion of entry into 68Ga-FAPI-46 study and completion of scan. Hematologic parameters defined as: Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 50,000/mm3 Hemoglobin ≥ 8 g/dL. Blood chemistry levels defined as: AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 3 times ULN Creatinine ≤ 3 times ULN Able to remain motionless for up to 30-60 minutes per scan. Exclusion Criteria: Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA). Participants with Class 3 or 4 NYHA Congestive Heart Failure. Clinically significant bleeding within two weeks prior to trial entry (e.g. gastrointestinal bleeding, intracranial bleeding). Pregnant or lactating women. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e. larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to study day 1 or anticipated surgery within the subsequent 6 weeks. Has an additional active malignancy requiring therapy within the past 2 years. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. Psychiatric illness/social situations that would interfere with compliance with study requirements Cannot undergo PET/CT scanning because of weight limits (350 lbs). INR>1.2; PTT>5 seconds above UNL.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 177Lu-DOTA-EB-FAPI<br>177Lu-DOTA-EB-FAPI A maximum of 2 cycles of 100 mCi (3.7 GBq) 177Lu-DOTA-EB-FAPI, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks | Drug: 177Lu-DOTA-EB-FAPI radionuclide therapy<br>* radionuclide therapy using 177Lu-DOTA-EB-FAPI 100 mCi (3.7 GBq) will be performed 6-weekly. A maximum of 2 cycles will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-related adverse events (safety and tolerability) | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. Dose-limiting toxicity was defined as any 177Lu-DOTA-EB-FAPI-related AE ≥ grade 3 (G3). For Hemoglobin < 8.0 g/dL; < 4.9 mmol/L; < 80 g/L; Need blood transfusion heal. Severe hypocytosis or with this age group The total number of normal cells was reduced >50% and ≤75%. | At the end of Cycle 2 (each cycle is 42 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | 68Ga-Fibroblast activation protein inhibitor 46 will be performed for efficacy evaluation by RECIST 1.1. Particularly, 68Ga-FAPI-46 will be performed at baseline, and 6 weeks after two treatment cycles. | At the end of Cycle 2 (each cycle is 42 days) | 
| Dosimetry | Dosimetry, measured as absorbed dose in tumor and normal organs (Gy/GBq), was estimated in the first treatment cycle for each patient. | At the end of Cycle 1 (each cycle is 42 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory solid tumor, Radioligand therapy, 177Lu-DOTA-EB-FAPI