Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

NCT06008119 | Recruiting Phase 3

• 1 other identifier: HL-085-304
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, open-label, Phase 3 study

Conditions

Colorectal Cancer Metastatic

Keywords

BRAFV600E mutant

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  defined as the time from first dose to the earliest documented disease progression or death due to any cause

  up to 12 months

Secondary Outcomes (4)

• Overall Survival（OS）

  up to 12 months

• Overall Response Rate（ORR）

  up to 12 months

• Duration of Response（DOR）

  up to 12 months

• Disease control rate (DCR)

  up to 12 months

Study Arms (2)

Experimental

EXPERIMENTAL

Tunlamatinib plus Vemurafenib

Drug: Tunlametinib plus Vemurafenib

Control

ACTIVE COMPARATOR

Investigators' choice

Drug: Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab

Interventions

Tunlametinib plus Vemurafenib DRUG

12mg BID Tunlametinib+720mg BID Vemurafenib

Experimental

Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab DRUG

According to investigators' suggestion

Control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures.
• Male or female patients with 18 to 70 years of age at time of informed consent;
• Histological or cytologically confirmed metastatic CRC
• Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory (BRAFV600 is permitted)
• Able to provide a sufficient amount of representative tumor specimen (primary or metastatic, archival or newly obtained) for confirmatory central laboratory testing of BRAF mutation status.
• Progression of disease after 1 or more prior regimens in the metastatic setting
• At least 1 site of radiographically measurable disease by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 1;
• Life expectancy ≥ 3 months;
• Can swallow the medicine,
• Adequate hematologic, renal, cardiac and liver function as defined by laboratory values performed within 7 days prior to initiation of dosing:
• Be willing and able to complete all the study procedures and follow-up examinations.

You may not qualify if:

• Prior treatment with any BRAF and MEK inhibitor;
• Known contraindication to receive the treatment of control arm (according to latest PI).
• Symptomatic brain metastasis or leptomeningeal disease
• History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
• Known history of acute or chronic pancreatitis
• Uncontrolled GI bleeding, Dysphagia，refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
• Serious cardiovascular disease , including uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia , deep vein thrombosis or pulmonary emboli or cerebrovascular events ≤ 6 months prior to starting study treatment;
• History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
• Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Uncontrolled blood pressure despite medical treatment
• Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
• Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy
• Anti-HIV(+) , Anti-TP( +); Active hepatitis B or hepatitis C infection …….

Sponsors & Collaborators

• Shanghai Kechow Pharma, Inc.: lead

Study Sites (1)

Beijing Oncology Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Interventions

Vemurafenib

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 23, 2023
• Study Start: October 25, 2023
• Primary Completion (Estimated): December 24, 2026
• Study Completion (Estimated): December 24, 2026
• Last Updated: September 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)