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An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600E-mutant Non-small Cell Lung Cancer

NCT03915951

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600E-mutant Non-small Cell Lung Cancer
  • Official Title: A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600E-mutant Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: ARRAY-818-202
  • NCT ID: NCT03915951

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
encorafenibTreatment Period
binimetinibTreatment Period

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Treatment PeriodExperimentalStudy 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)
  • encorafenib
  • binimetinib

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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time Frame:Up to 24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Progression-free Survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence and severity of adverse events (AEs)
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Array BioPharma

Trial Keywords

  • lung cancer
  • cancer
  • non-small cell lung cancer

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