Cetuximab in Combination With Dabrafenib and Tislelizumab in BRAF Mutated Treatment of Advanced Colorectal Cancer

Cetuximab in Combination With Dabrafenib and Tislelizumab in BRAF Mutated Treatment of Advanced Colorectal Cancer: a Prospective, Exploratory, Phase II Clinical Study

To explore the efficacy and safety of Cetuximab in combination with dabrafenib and Tislelizumab in BRAF mutated treatment of advanced colorectal cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Colorectal Cancer
• Intervention / Treatment: Drug: Cetuximab Dabrafenib Tislelizumab

Detailed Description

Due to Encorafenib has not been marketed in China, it is difficult to benefit patients, and there are no reported studies of Dabrafenib, also a BRAF inhibitor, in combination with anti-EGFR monoclonal antibody and immunotherapy in BRAF mutated mCRC. Therefore, we intend to use Dabrafenib in combination with cetuximab and Tislelizumab in the treatment of BRAF V600E mutated patients with advanced colorectal cancer to observe the initial efficacy and safety.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wangxia Lv; Phone Number: 13757141026; Email: lvwangxia@163.com

Study Locations

• China
  • Zhejing
    • Hangzhou, Zhejing, China
      • Zhejiang Cancer Institute & Hospital
      • Contact: Wangxia Lv; Phone Number: 13757141026; Email: lvwangxia@163.com
      • Sub-Investigator: Meiqin Yuan
      • Sub-Investigator: Bixia Liu
      • Sub-Investigator: Zhong Shi
      • Sub-Investigator: Junchi Cheng
      • Principal Investigator: Hanjun Zhong
      • Sub-Investigator: Yazhen Zhao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Histopathological diagnosis of advanced colorectal cancer; 2. Previous first-line standard treatment failed or could not tolerate first-line standard treatment; 3. BRAF V600E mutation (NGS or ARMS-PCR assay); 4.18 years old≤ Age≤75 years old; 5. PS score 0-1; 6. At least one measurable or evaluable lesion according to RECIST v1.1; 7. Baseline color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥60%; 8. Has adequate organ and bone marrow function; 9. Expected survival ≥12 weeks 10. Female subjects of childbearing age or male subjects whose sexual partner is a female of childbearing age are required to take effective contraceptive measures throughout the treatment period and for 6 months after the treatment period 11. Sign a written informed consent and be able to comply with the visit and related procedures required by the program;

Exclusion Criteria:

• 1. Malignant diseases other than colorectal cancer diagnosed within 5 years prior to first administration (excluding radical treatment)Carcinomas in situ with sexual resection); 2. Currently participating in the intervention clinical study treatment, or receiving other study drugs or using study devices within 4 weeks before the first dose; 3. Previous treatment with BRAF inhibitors, MEK inhibitors, anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs that target another stimulus or synergically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137); 4. Received systemic systemic treatment with Chinese patent drugs with anti-tumor indications or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural fluid) within 2 weeks before the first administration; 5. An active autoimmune disease requiring systemic treatment (e.g. with disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2 years prior to initial administration. Replacement therapies (such as thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy; 6. Were receiving systemic glucocorticoid therapy (excluding topical glucocorticoids by nasal spray, inhalation, or other route) or any other form of immunosuppressive therapy within 7 days prior to initial administration of the study 7. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation 8. Known allergy to any monoclonal antibody formulation ingredient (grade 3 or above allergic reaction) 9. Has not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or baseline, excluding weakness or hair loss); 10. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 11. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected greater than the upper limit of normal value in the laboratory of the study center); 12. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection); 13. Received live vaccine within 30 days prior to the first dose (cycle 1, day 1); 14. Pregnant or lactating women; 15. The presence of any serious or uncontrolled systemic disease 16. Medical history or evidence of disease that may interfere with test results, prevent participants from fully participating in the study, abnormal treatment or laboratory test values, or other conditions that the investigator considers unsuitable for enrollment The Investigator considers other potential risks unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Advanced CRC; Patients with BRAF Mutated Advanced CRC were given Cetuximab in Combination With Dabrafenib and Tislelizumab	Drug: Cetuximab Dabrafenib Tislelizumab; Dabrafenib 150mg，BID, Cetuximab 250mg/m2, Tislelizumab 200mg Treatment every three weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	CR + PR rate according to the RECIST version 1.1 guidelines.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival time	OS was calculated from the date of pharmacy to death from any cause.	up to 36 months
Progression Free Survival (PFS）	To assess the efficacy of Surufatinib Combine With Immunotherapy and Chemotherapy as second-line therapy to Advanced CRC, patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).	up to 12 months

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Principal Investigator: Wangxia Lv, Zhejiang Cancer Institute & Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Dabrafenib; Cetuximab; Tislelizumab
• Other Study ID Numbers: Braf-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No