An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: encorafenib; binimetinib
Intervention description: self-administered orally; self-administered orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 98.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lung cancer; cancer; non-small cell lung cancer; non small cell lung cancer; NSCLC; Encorafenib; Binimetinib; Phase 2; Open Label; BRAF mutation; BRAF V600E; Array; Stage IV NSCLC; Metastatic NSCLC; PDL1; PD-LI; Immunotherapy; First line platinum based chemotherapy; BRAF inhibitor; V600

Summary:

      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.
    

Eligibility criteria:

        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
             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.