Tislelizumab Combined With Fruquintinib for Metastatic pMMR/MSS Colorectal Cancer

Trial details

Who runs it

Sun Yat-sen University

Trial code

NCT05690035

Record updated

9 July 2024

Original description

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.Read full original descriptionShow less

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.

Inclusion: 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: 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; Have received other PD-1 antibody therapy or other immunotherapy targeting PD-1/PD-L1 in the past; Known hereditary or acquired bleeding and thrombophilia or being treated with thrombolysis or anticoagulation; Clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment; Live vaccine may be inoculated less than 4 weeks before the study medication or during the study period; Any active autoimmune disease or history of autoimmune disease; Severe allergic reaction to other monoclonal antibodies; 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; 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); 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; Subjects with clinical symptoms of untreated active brain metastasis or meningeal metastasis; Patients with high TMB (≥ 30Muts/Mb) and germline or somatic POLE/POLD1 gene mutations in the exonuclease domain; Urinary protein ≥ ++, or the 24-hour urine protein quantification greater than 1.0g.

ClinicalTrials.gov NCT05690035