Metastatic Colorectal Cancer Clinical Trial
Official title:
PD-1 Antibody (Tislelizumab) Combined With VEGFR 1/2/3 Inhibitor (Fruquintinib) for ARID1A-mutated Metastatic pMMR/MSS Colorectal Cancer: an Open-label, Multi-center, Phase II Clinical Trial
This is an open-label phase II study, with the aim of investigating the efficacy and safety of Tislelizumab + Fruquintinib combination therapy in ARID1A-mutated pMMR/MSS metastatic colorectal cancer who have been treated with standard chemotherapy that includes fluoropyrimidine, oxaliplatin, and irinotecan. Patients with hypermutated CRC that carries POLE/POLD1 mutations cannot be included.
Status | Not yet recruiting |
Enrollment | 12 |
Est. completion date | January 2026 |
Est. primary completion date | December 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | Inclusion Criteria: - 18-80 years old (including 18 and 80); - Histologically confirmed colorectal adenocarcinoma and biopsy pathology confirmed MSS/pMMR; - Gene testing confirmed ARID1A gene mutation (nonsynonymous); - No signs of intestinal obstruction; Or intestinal obstruction has been relieved after proximal colostomy; - Has received and failed = 2 line of chemotherapy or progressed on or intolerable to oxaliplatin, irinotecan and fluorouracil chemotherapy after diagnosed with mCRC; - ECOG PS 0-2; - Able to swallow tablets; - Life expectancy of greater than 3 months; - Adequate bone marrow and organ function; - If female and of childbearing potential, must: - Have a negative pregnancy test =14 days prior to initiating study treatment - Agree to avoid pregnancy during and for 3 months after study treatment If male with a partner of childbearing potential, must: - Agree to use adequate, medically approved, contraceptive precautions during and for 3 months after the last dose of study treatment. - Able and willing to provide written informed consent for the study. Exclusion Criteria: - Any active autoimmune disease or history of autoimmune disease; - Those who are using immunosuppressive agents, or systemic or absorbable local hormone therapy to achieve immunosuppressive purpose, and continue to use within 2 weeks before enrollment; - Severe allergic reaction to other monoclonal antibodies; - Subjects with clinical symptoms of untreated active brain metastasis or meningeal metastasis; - Have received other PD-1 antibody therapy or other immunotherapy targeting PD-1/PD-L1 in the past; - Patients with high TMB (= 30Muts/Mb) and germline or somatic POLE/POLD1 gene mutations in the exonuclease domain; - There are clinical symptoms or diseases of heart that are not well controlled, such as: (a) heart failure of NYHA level 2 or above (b) unstable angina pectoris (c) myocardial infarction occurred within 1 year (d) clinically significant supraventricular or ventricular arrhythmia needs treatment or intervention; - Known hereditary or acquired bleeding and thrombophilia or being treated with thrombolysis or anticoagulation; - Urinary protein = ++, or the 24-hour urine protein quantification greater than 1.0g; - Clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment; - Subjects with active infection; - Congenital or acquired immune deficiency (such as HIV infected persons), or active hepatitis (hepatitis B: HBsAg positive and HBV DNA = 10^4 copies/ml; hepatitis C: HCV antibody positive); - Other advanced malignant tumors within 5 years (except cured skin basal cell carcinoma, cervical carcinoma in situ, ovarian cancer, thyroid cancer and breast cancer); - Live vaccine may be inoculated less than 4 weeks before the study medication or during the study period; - Known or suspected to be allergic to the study drug or to any drug given in this trial; - Have any other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other conditions that makes the subject not eligible according to the judgment of the investigator. |
Country | Name | City | State |
---|---|---|---|
China | Sun Yat-sen University, Cancer Center | Guangzhou | Guangdong |
China | Xiaoshi Zhang | Guangzhou |
Lead Sponsor | Collaborator |
---|---|
Sun Yat-sen University | BeiGene, Hutchmed |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Objective Response Rate (ORR) | The proportion of patients with a confirmed complete response or partial response | up to 3 years | |
Secondary | Progression-Free Survival (PFS) | PFS is defined as the time from enrollment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. | up to 3 years | |
Secondary | Overall Survival (OS) | OS is defined as the time from enrollment to death due to any cause. | up to 3 years | |
Secondary | Disease control rate | The proportion of patients with a best overall response of confirmed complete or partial response, or stable disease (CR+ PR + SD). | up to 3 years | |
Secondary | Incidence of Treatment-Emergent Adverse Events | Safety and tolerance evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0. | until 60 days after last patient last study drug treatment |
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