RWF_2020000039

Encorafenib/Binimetinib With or Without Nivolumab for Patients With Metastatic BRAF V600 Mutant Thyroid Cancer

This phase II trial studies how well encorafenib and binimetinib given with or without nivolumab works in treating patients with BRAF V600 mutation positive thyroid cancer that has spread to other places in the body (metastatic) and does not respond to radioiodine treatment (refractory). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The trial aims to find out if the combination of encorafenib and binimetinib, with and without study nivolumab, is a safe and effective way to treat metastatic radioiodine refractory thyroid cancer.

Inclusion Criteria:
• Histologically (or cytologically) confirmed diagnosis of metastatic, radioiodine (RAI) refractory, BRAFV600E/M mutant differentiated thyroid cancer (DTC)
• Measurable disease
• Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
• Triplicate average baseline corrected QT (QTc) interval =< 480 ms

Exclusion Criteria:
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational agent/device within 4 weeks of first dose of study intervention
• Participants with active, known, or suspected autoimmune disease.
• Prior treatment with selective/potent BRAF/MEK inhibitors including vemurafenib, dabrafenib, encorafenib, selumetinib, trametinib, cobimetinib, binimetinib.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody
• History of allergy or hypersensitivity to any monoclonal antibody
• History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO; history of retinal degenerative disease
• Previous or concurrent malignancy within 3 years of study entry
• Impaired cardiovascular function or clinically significant cardiovascular diseases
• History of thromboembolic or cerebrovascular events =< 12 weeks prior to the first dose of study treatment.
• Known history of acute or chronic pancreatitis
• Impaired gastrointestinal function or disease that may significantly alter the absorption of encorafenib or binimetinib
• Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase (CK)
• Current use of a prohibited medication (including herbal medications, supplements, or foods), as described, or use of a prohibited medication =< 1 week prior to the start of study treatment
• Participants who have undergone major surgery (e.g., intracranial, intrathoracic, or intra-abdominal surgery) =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
Phase II
NCT04061980
Oncology
Endocrine
Matthew Taylor, M.D.
Earle A Chiles Research Institute (EACRI)
George Morris
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Clackamas Clinic
  • Providence Cancer Institute Franz Clinic
  • Providence Cancer Institute Newberg Clinic