Tislelizumab Combined With Fruquintinib for Metastatic pMMR/MSS Colorectal Cancer

NCT ID: NCT05690035

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-31
• Study Completion Date: 2025-07-31

Brief 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 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.

Detailed Description

In this open-label phase II study, patients with ARID1A-mutated pMMR/MSS metastatic colorectal cancer who have been treated with standard chemotherapy that includes fluoropyrimidine, oxaliplatin, and irinotecan, will be scheduled for Tislelizumab (200mg ivdrip Q3W day1) + Fruquintinib (5mg/day Q3W day1-14) until intolerable toxicity, disease progression or death. Primary endpoint of this study is ORR and secondary endpoints are OS, PFS, DCR and safety.

Conditions

Metastatic Colorectal Cancer; mCRC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

patients with mCRC

Tislelizumab 200mg ivdrip every 3 weeks; Fruquintinib 5mg qd day 1-14, every 3 weeks

Group Type: EXPERIMENTAL

Tislelizumab & Fruquintinib

Intervention Type: DRUG

combinational treatment of Tislelizumab and Fruquintinib until PD, intolerable toxicity, death or withdrawal of informed consent

Interventions

Tislelizumab & Fruquintinib

combinational treatment of Tislelizumab and Fruquintinib until PD, intolerable toxicity, death or withdrawal of informed consent

Intervention Type: DRUG

Eligibility 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);
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchmed

INDUSTRY

Sponsor Role: collaborator

BeiGene

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Pei-Rong Ding

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peirong Ding, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University, Cancer Center

Guangzhou, Guangdong, China

Xiaoshi Zhang

Guangzhou, , China

Countries

China

Other Identifiers

SL-B2022-653-01

Identifier Type: -

Identifier Source: org_study_id