Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib +
cetuximab plus or minus binimetinib versus Investigator's choice of either
irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose
disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study
contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib +
binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.
Phase
Phase 3
Funding Agency/Sponsor
Industrial
Disease
Colorectal Cancer
Enrollment Eligibility
Key Inclusion Criteria:
- Age ≥ 18 years at time of informed consent
- Histologically- or cytologically-confirmed CRC that is metastatic
- Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any
time prior to Screening or by the central laboratory
- Progression of disease after 1 or 2 prior regimens in the metastatic setting
- Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1
- Adequate bone marrow, cardiac, kidney and liver function
- Able to take oral medications
- Female patients are either postmenopausal for at least 1 year, are surgically sterile
for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy
from screening through follow-up if of childbearing potential
- Males must agree to take appropriate precautions to avoid fathering a child from
screening through follow-up
Key Exclusion Criteria:
- Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other
epidermal growth factor receptor (EGFR) inhibitors
- Prior irinotecan hypersensitivity or toxicity that would suggest an inability to
tolerate irinotecan 180 mg/m2 every 2 weeks
- Symptomatic brain metastasis or leptomeningeal disease
- 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)
- Known history of acute or chronic pancreatitis
- History of chronic inflammatory bowel disease or Crohn's disease requiring medical
intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months
prior to randomization
- Uncontrolled blood pressure despite medical treatment
- Impaired GI function or disease that may significantly alter the absorption of
encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting,
malabsorption syndrome, small bowel resection with decreased intestinal absorption)
- 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
- History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study
treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein
thrombosis or pulmonary emboli
- 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)
- 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
- Known history of HIV infection
- Active hepatitis B or hepatitis C infection
- Known history of Gilbert's syndrome
- Known contraindication to receive cetuximab or irinotecan at the planned doses