Tislelizumab Combined With Fruquintinib for Metastatic pMMR/MSS Colorectal Cancer

NCT05690035 | Withdrawn Phase 2

• 1 other identifier: SL-B2022-653-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Metastatic Colorectal Cancer; mCRC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of patients with a confirmed complete response or partial response

  up to 3 years

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  up to 3 years

• Overall Survival (OS)

  up to 3 years

• Disease control rate

  up to 3 years

• Incidence of Treatment-Emergent Adverse Events

  until 60 days after last patient last study drug treatment

Study Arms (1)

patients with mCRC

EXPERIMENTAL

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

Drug: Tislelizumab & Fruquintinib

Interventions

Tislelizumab & Fruquintinib DRUG

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

patients with mCRC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Hutchmed: collaborator
• BeiGene: collaborator

Study Sites (2)

Sun Yat-sen University, Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Xiaoshi Zhang

Guangzhou, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

tislelizumab; HMPL-013

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Peirong Ding, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: January 19, 2023
• Study Start: July 1, 2025
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)