Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer
Study Details
Study Description
Brief Summary
This is a multicenter, randomized, open-label, 3-arm Phase 3 study
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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
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
- Progression-free Survival (PFS) [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
- Overall Survival（OS） [up to 12 months]
defined as the time from the date of taking drugs to the date of death due to any cause
- Overall Response Rate（ORR） [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
- Duration of Response（DOR） [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)
- Disease control rate (DCR) [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
Criteria
Inclusion Criteria:
- Inclusion Criteria:
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Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures.
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Male or female patients with 18 to 70 years of age at time of informed consent;
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Histological or cytologically confirmed metastatic CRC
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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)
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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.
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Progression of disease after 1 or more prior regimens in the metastatic setting
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At least 1 site of radiographically measurable disease by RECIST 1.1
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Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 1;
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Life expectancy ≥ 3 months;
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Can swallow the medicine,
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Adequate hematologic, renal, cardiac and liver function as defined by laboratory values performed within 7 days prior to initiation of dosing:
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Be willing and able to complete all the study procedures and follow-up examinations.
Exclusion Criteria:
- Exclusion Criteria:
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Prior treatment with any BRAF and MEK inhibitor;
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Known contraindication to receive the treatment of control arm (according to latest PI).
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Symptomatic brain metastasis or leptomeningeal disease
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History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
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Known history of acute or chronic pancreatitis
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Uncontrolled GI bleeding, Dysphagia，refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
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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;
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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)
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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)
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Uncontrolled blood pressure despite medical treatment
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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
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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
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Anti-HIV(+) , Anti-TP( +); Active hepatitis B or hepatitis C infection …….
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Shanghai Kechow Pharma, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HL-085-304