An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer

• Status: Recruiting
• Trial end date: 2024-03-17
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Array BioPharma; Pfizer

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.

• 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.