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

A Multicenter, Randomized, Open-label, Phase 3 Study to Evaluate the Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

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

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: Tunlametinib plus Vemurafenib; Drug: Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab

Detailed Description

This is a multicenter, randomized, open-label, Phase 3 study to evaluate Tunlamatinib plus Vemurafenib versus Investigator's choice of Chemotherapy based treatment as controls in patients with BRAFV600E mutant Metastatic Colorectal Cancer (CRC) whose disease has progressed after 1 or more prior regimens in the metastatic setting.

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Oncology Hospital
      • Contact: Lin Shen; Phone Number: 86+10-88196561; Email: doctorshenlin@sina.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Inclusion Criteria:

  1. Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures.
  2. Male or female patients with 18 to 70 years of age at time of informed consent;
  3. Histological or cytologically confirmed metastatic CRC
  4. 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)
  5. 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.
  6. Progression of disease after 1 or more prior regimens in the metastatic setting
  7. At least 1 site of radiographically measurable disease by RECIST 1.1
  8. Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 1;
  9. Life expectancy ≥ 3 months;
  10. Can swallow the medicine,
  11. Adequate hematologic, renal, cardiac and liver function as defined by laboratory values performed within 7 days prior to initiation of dosing:
  12. Be willing and able to complete all the study procedures and follow-up examinations.

Exclusion Criteria:

• Exclusion Criteria:

  1. Prior treatment with any BRAF and MEK inhibitor;
  2. Known contraindication to receive the treatment of control arm (according to latest PI).
  3. Symptomatic brain metastasis or leptomeningeal disease
  4. History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
  5. Known history of acute or chronic pancreatitis
  6. Uncontrolled GI bleeding, Dysphagia，refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
  7. 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;
  8. 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)
  9. 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)
  10. Uncontrolled blood pressure despite medical treatment
  11. 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
  12. 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
  13. Anti-HIV(+) , Anti-TP( +); Active hepatitis B or hepatitis C infection …….

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Tunlamatinib plus Vemurafenib	Drug: Tunlametinib plus Vemurafenib; 12mg BID Tunlametinib+720mg BID Vemurafenib
Active Comparator: Control; Investigators' choice	Drug: Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab; According to investigators' suggestion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate（ORR）	Defined as the proportion of subjects with an optimal response of CR or PR over the course of the study from enrollment to disease progression	up to 12 months
Duration of Response（DOR）	Defined as the time from the first CR or PR evaluation of tumor efficacy to the first occurrence of PD or death from any cause (whichever occurs first)	up to 12 months
Disease control rate (DCR)	roportion of subjects with response defined as CR, PR, and SD throughout the study from subjects first dose to disease progression or death	up to 12 months
Overall Survival（OS）	defined as the time from the date of taking drugs to the date of death due to any cause. After disease progression, participants in the control group can crossover to receive the experimental drug treatment if they meet the crossover enrollment criteria. The median survival time of the two groups will be estimated by Kaplan-Meier method, and the hazard ratio (HR) between the two groups will be estimated use the Cox proportional hazards model in FAS, and OS will be adjusted using the following two methods: Rank Preserving Structural Failure Time Model (RPSFTM): Corrects survival outcomes for treatment crossover from the control group to the experimental group by estimating counterfactual survival times to infer the treatment effect without crossover.; Inverse Probability of Censoring Weighting (IPCW): Adjusts for informative censoring bias caused by treatment crossover. The weights will be derived from time-dependent censoring models.	up to 12 months

Collaborators and Investigators

• Sponsor: Shanghai Kechow Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Estimated): December 24, 2026
• Study Completion (Estimated): December 24, 2026

Study Registration Dates

• First Submitted: August 8, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: BRAFV600E mutant
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Indoles; Sulfonamides; Sulfones; Vemurafenib
• Other Study ID Numbers: HL-085-304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No