Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With

• Status: Active, not recruiting
• Trial end date: 2022-05-31
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Array BioPharma; Pfizer
• Collaborators: Merck KGaA; Merck KGaA, Darmstadt, Germany; Ono Pharmaceutical Co. Ltd; Pierre Fabre Medicament
• Treatments: Camptothecin; Cetuximab; Fluorouracil; Folic Acid; Irinotecan; Leucovorin; Levoleucovorin

Criteria

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