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

• ClinicalTrials.gov Identifier: NCT06008119
• Recruitment Status: Not yet recruiting
• First Posted: August 23, 2023
• Last Update Posted: August 23, 2023
• Sponsor: Shanghai Kechow Pharma, Inc.
• Information provided by (Responsible Party): Shanghai Kechow Pharma, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer Metastatic	Drug: Tunlametinib plus Vemurafenib; Drug: Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab	Phase 3

Detailed Description:

This is a multicenter, randomized, open-label, 3-arm 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 165 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: November 24, 2023
• Estimated Primary Completion Date: December 24, 2026
• Estimated Study Completion Date: December 24, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: up to 12 months ]
   defined as the time from first dose to the earliest documented disease progression or death due to any cause

Secondary Outcome Measures :

1. Overall Survival（OS） [ Time Frame: up to 12 months ]
   defined as the time from the date of taking drugs to the date of death due to any cause
2. Overall Response Rate（ORR） [ Time Frame: up to 12 months ]
   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
3. Duration of Response（DOR） [ Time Frame: up to 12 months ]
   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)
4. Disease control rate (DCR) [ Time Frame: up to 12 months ]
   roportion of subjects with response defined as CR, PR, and SD throughout the study from subjects first dose to disease progression or death

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 …….

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Shanghai Kechow Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT06008119
• Other Study ID Numbers: HL-085-304
• First Posted: August 23, 2023
• Last Update Posted: August 23, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shanghai Kechow Pharma, Inc.:

BRAFV600E mutant

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Bevacizumab; Cetuximab; Vemurafenib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action