FAPI PET for Response Evaluation and Prognosis Prediction in Liver and Biliary Cancer Patients Treated With PD-1 Combination Therapy

Study Overview
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Brief Summary
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The purpose of this study is to explore the ability of positron emission tomography (PET) with [68Ga]FAPI to detect, evaluate treatment response, and predict prognosis in advanced liver and biliary cancer patients treated with anti-PD-1 antibodies-based combination therapy.

Detailed Description
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Hepatocellular carcinoma (HCC) and bile tract cancers (BTC) are major health issue worldwide, particularly in Eastern Asia. Anti-PD-1 antibodies-based combination therapy has shown considerable efficacy in advanced HCC and BTC. However, an objective response is only achieved in a portion of patients. Thus, there is an urgent need for better patient selection before immunotherapy as well as accurate evaluation of treatment response. PET is a noninvasive imaging technique which might be an effective tool for evaluating anti-PD-1 antibody-based combination treatment in liver and biliary cancer. 68Ga-FAPI has been developed as a novel agent targeting fibroblast activation protein (FAP) that is overexpressed in cancer-associated fibroblasts in liver and biliary cancer. Prior studies have shown that FAP-expressing CAF suppresses anti-tumor immunity while suppressing FAP can overcome stromal barriers to immuno-oncological responses. Meanwhile, 68Ga-FAPI PET showed a high detection rate in primary and metastatic lesions in liver and biliary cancer. The aim of this study is to evaluate the ability of positron emission tomography (PET) with [68Ga]FAPI to detect, evaluate treatment response, and predict prognosis in advanced liver and biliary cancer patients treated with anti-PD-1 antibodies-based combination therapy. Our hypothesis is that baseline [68Ga]FAPI PET parameters can predict response and clinical benefit of anti-PD-1 antibodies-based combination therapy and overall survival; that effects of anti-PD-1 antibodies-based combination therapy in liver and biliary cancer can be detected and quantified by [68Ga]FAPI PET after treatment in correlation with other radiological findings and clinical endpoints; that such effects are more prominent with [68Ga]FAPI PET than with the traditional [18F]FDG PET.

Official Title
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68Ga-FAPI PET for Response Evaluation and Prognosis Prediction in Advanced Liver and Biliary Cancer Patients Treated With PD-1 Based Combination Therapy: A Head-to-head Comparison to 18F-FDG PET

Conditions
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Hepatocellular Carcinoma, Bile Duct Cancer

Intervention / Treatment
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* Diagnostic Test: [68Ga]FAPI PET/CT and [18F]FDG PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: locally advanced or metastatic and/or unresectable HCC or BTC Child Pugh A or B liver function status an ECOG performance status score of 0-2 Exclusion Criteria: intolerance to anti-PD-1-based combination therapy active or prior autoimmune disease concurrent use of immunosuppressive medicaments

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: [68Ga]FAPI PET/CT and [18F]FDG PET/CT|To perform [68Ga]FAPI PET/CT and [18F]FDG PET/CT in patients with advanced liver and biliary cancer before and after treatment with PD-1 Based Combination Therapy|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline SUVmax on [68Ga]FAPI and [18F] FDG PET Scans | Baseline FAPI and FDG SUVmax, fibro-activation tumor volume (metabolic tumor volume), total lesion fibro-activation (total lesion glycolysis) before treatment were determined. | through study completion, an average of 2 years | 
| Baseline active tumor volume on [68Ga]FAPI and [18F] FDG PET Scans | Baseline fibro-activation tumor volume and metabolic tumor volume before treatment were determined. | through study completion, an average of 2 years | 
| Baseline total lesion activation on [68Ga]FAPI and [18F] FDG PET Scans | Baseline total lesion fibro-activation and total lesion glycolysis before treatment were determined. | through study completion, an average of 2 years | 
| Response of SUVmax to anti-PD1-based combination therapy shown in [68Ga]FAPI and [18F] FDG PET Scans | Changes in FAPI and FDG SUVmax during treatment were determined. | through study completion, an average of 1 years | 
| Response of active tumor volume to anti-PD1-based combination therapy shown in [68Ga]FAPI and [18F] FDG PET Scans | Changes in fibro-activation tumor volume and metabolic tumor volume during treatment were determined. | through study completion, an average of 1 years | 
| Response of total lesion activation to anti-PD1-based combination therapy shown in [68Ga]FAPI and [18F] FDG PET Scans | Changes in total lesion fibro-activation and total lesion glycolysis during treatment were determined. | through study completion, an average of 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response evaluated by CT and MRI | Tumor response was reported per Response Evaluation Criteria in Solid Tumors (RECIST) criteria | through study completion, an average of 1 years | 
| Overall survival after treatment | Overall survival after treatment | through study completion, an average of 2 years | 
| Progression-free survival after treatment | Progression-free survival after treatment | through study completion, an average of 2 years |