TAS-102 Combined With Bevacizumab and Tislelizumab Third-line or Above in the Treatment of Liver Metastasis in Colorectal Cancer

Study Overview
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Brief Summary
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To evaluate the clinical efficacy and safety of TAS-102 combined with bevacizumab and tislelizumab in third-line or above treatment in patients with advanced colorectal adenocarcinoma with liver metastasis.

Official Title
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TAS-102 Combined With Bevacizumab and Tislelizumab Third-line or Above in the Treatment of Liver Metastasis in Colorectal Cancer : An Open-label 、Phase Ⅱ Clinical Trial

Conditions
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Immunotherapy, Colorectal Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: bevacizumab
* Drug: TAS-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who provided informed consent and voluntarily enrolled Patients with liver metastasis of advanced colorectal adenocarcinoma with MSS confirmed by pathology; 18-75 years old; Measurable target lesions according to RECIST V1.1 assessment criteria; Progression after standard second-line treatment (irinotecan, oxaliplatin, or fluorouracil); 0   2 points according to ECOG quality of life score; Drugs can be taken orally Estimated survival ≥3 months; Women of childbearing age should comply with contraceptive measures if pregnancy test is negative; Ascites with no obvious symptoms and no clinical intervention; Adequate organ and bone marrow functions, ecg, blood, biochemical and other basic tests are not contraindications of chemotherapy; Adherence to scheduled visits, treatment plans, laboratory tests, and other study procedures Willingness and ability. Exclusion Criteria: Previous application of TAS-102; Pregnant or lactating women; No contraception during the reproductive period; patients known to have a history of allergy to any study drug, similar drug or excipient; Patients with risk of massive gastrointestinal bleeding or gastrointestinal obstruction; Patients with a history of thromboembolism, except those caused by PICC; Patients with active infection; Patients with uncontrolled hypertension (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90) MmHg); Patients with brain metastases with clinical symptoms or imaging evidence; Contraindications for treatment of other chronic diseases; Previous immunotherapy-related myocarditis, pneumonia, colitis, hepatitis, kidney Inflammation and other conditions, the current AE is still ≥2; According to THE NCI CTCAE 5.0 assessment criteria, there are all types of existing cases due to previous treatment Patients with grade ≥2 toxic reactions; Other conditions that the investigator determines are not suitable for inclusion in the study. Received any anti-tumor therapy and participated in other clinical studies within 4 weeks prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: TAS-102 combined with bevacizumab and tislelizumab<br>TAS-102 combined with bevacizumab and tislelizumab third-line or above in the treatment of liver metastasis in colorectal cancer | Drug: Tislelizumab<br>* Participants will receive Tislelizumab, 200mg, intravenously over 30 - 60 minutes, day 1 of every 3 weeks<br>Drug: bevacizumab<br>* Participants will receive bevacizumab，5mg/kg，intravenously over 60 - 90 minutes, day 1 and day 15 of every 4 weeks<br>Drug: TAS-102<br>* Participants will receive TAS-102, 35mg/m2, bid，d1-d5, d8-d12 of every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | Time from enrollment to the onset of disease progression or death. | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate Determine the tumor shrinkage rate, tumor boundary and the adhesion of tumor | every 8 weeks (up to 24 months) |