Tislelizumab Combined With Fruquintinib for Metastatic pMMR/MSS Colorectal Cancer

• Status: Not yet recruiting
• Trial end date: 2026-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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 whose tumor progressed after two or more lines of chemotherapy. Patients with hypermutated CRC that carries POLE/POLD1 mutations cannot be included.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Collaborators: BeiGene; Hutchmed

Criteria

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 mutation);

• 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;

• Hypertension beyond control defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg;

• 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;

• 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;

• Artery/vein thrombosis occurred within 6 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.