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

Pfizer

Status and phase: Active, not recruiting; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: encorafenib; Drug: binimetinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03915951

C4221008 (Other Identifier)

2019-000417-37 (EudraCT Number)

ARRAY-818-202

Details and patient eligibility

About

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.

Enrollment: 98 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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98 participants in 1 patient group

Treatment Period

Experimental group

Description:

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)

Treatment:

Drug: binimetinib

Drug: encorafenib