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

Other illness

• Exclusion Criteria:
  • 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 …….

• Inclusion Criteria:
  • 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.