Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

This is an interventional treatment trial for Advanced Solid Tumors focused on measuring solid tumor, melanoma Read More

Key Inclusion Criteria - Patients must meet all of the inclusion criteria to be eligible for enrollment into the study:

• Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC or IV; or other BRAF V600-mutant advanced solid tumors
• Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to enrollment, as determined using a local test;
• Evidence of measurable or non-measurable lesions
• Patient with unresectable locally advanced or metastatic melanoma who has received no prior treatment or progressed on or after prior systemic therapy; Note: Prior therapy with a BRAF proto-oncogene serine-threonine protein kinase (BRAF) inhibitor and/or a mitogen-activated protein (MAP) kinase (MEK) inhibitor is permitted except in the regimen immediately prior to study entry
• Patient with other (non-melanoma) BRAF V600E and/or V600K -mutant advanced solid tumors who has progressed on standard therapy or for whom there are no available standard therapies; Note: Prior therapy with a BRAF inhibitor and/or a MEK inhibitor is permitted except in the regimen immediately prior to study entry
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Adequate bone marrow, hepatic and renal function as specified in the protocol
• ARM 1 ONLY: Non-smoker who has not used nicotine containing products for at least 3 months prior to the first dose.

Key Exclusion Criteria - Patients meeting any of the following criteria are not eligible for enrollment in the study:

• Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable, with imaging (e.g., magnetic resonance imaging [MRI] or computed tomography [CT] demonstrating no current evidence of progressive brain metastases at screening);
• Symptomatic or untreated leptomeningeal disease;
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes);
• Clinically significant cardiac disease
• Known hyper-coagulability risks other than malignancy (e.g., Factor V Leiden syndrome);
• Thromboembolic event except catheter-related venous thrombosis ≤ 12 weeks prior to starting study treatment.
• Discontinuation of prior BRAF and/or MEK inhibitor treatment due to left ventricular dysfunction, pneumonitis/interstitial lung disease, or retinal vein occlusion;
• ARM 1 ONLY: Positive urine cotinine test at screening

• ARM 3 ONLY:

  • History of psychosis, depression or mania;
  • History of angioedema;
  • History of mitral valve prolapse;
  • History of left ventricular hypertrophy;