A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients with BRAFV600-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.
Key Inclusion Criteria:
- 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 or the presence of other BRAFV600 mutations other than V600E (i.e. K
or D) will be considered
- 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.
Key Exclusion Criteria:
- 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
- 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
- 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.