An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600E-mutant Non-small Cell Lung Cancer
This is an open-label, multicenter, non-randomized, Phase 2 study to determine the safety, tolerability and efficacy of encorafenib given in combination with binimetinib in patients with BRAFV600E-mutant metastatic non-small cell lung cancer (NSCLC). Patients who are either treatment-naïve, OR who have received 1) first-line treatment with standard platinum-based chemotherapy, OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy will be enrolled.
- Non-small Cell Lung Cancer
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is currently Stage IV. - Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local laboratory assay. - Patients who are either treatment-naïve (e.g., no prior systemic therapy for advanced/metastatic disease), OR who have received 1) first-line platinum-based chemotherapy OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1(PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy. - Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). - Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1. - Adequate bone marrow function characterized by the following at screening: - absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; - Platelets ≥ 100 × 10⁹/L; - Hemoglobin ≥ 8.5 g/dL (with or without blood transfusions). - Adequate hepatic and renal function characterized by the following at screening: - Total bilirubin ≤ 1.5 × upper limit of normal (ULN) - alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases; Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m².
- Patients who have documentation of any of the following: - epidermal growth factor receptor (EGFR) mutation - anaplastic lymphoma kinase (ALK) fusion oncogene or - ROS1 rearrangement - Patients who have received more than 1 prior line of systemic therapy in the advanced/metastatic setting. - Previous treatment with any BRAF inhibitor (e.g., dabrafenib, vemurafenib, XL281/BMS-908662, etc.), or any mitogen-activated protein kinase (MEK) inhibitor (e.g., trametinib, cobimetinib, selumetinib, RDEA119, etc.) prior to screening and enrollment. - Impaired cardiovascular function or clinically significant cardiovascular diseases - History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli. - 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); history of retinal degenerative disease. - Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phospho)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). - Patients with symptomatic brain metastasis, leptomeningeal disease or other active central nervous system (CNS) metastases are not eligible.
- Phase 2
- Study Type
- Intervention Model
- Single Group Assignment
- Primary Purpose
- None (Open Label)
|Study treatment with encorafenib and binimetinib will be self-administered orally without regard to food. Patients will receive the following per 28-day (± 3 days) cycle: Encorafenib: 450 mg (6 × 75 mg capsule) once daily (QD) Binimetinib: 45 mg (3 × 15 mg tablet) twice daily (BID)||
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