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

• ClinicalTrials.gov Identifier: NCT03915951
• Recruitment Status: Active, not recruiting
• First Posted: April 16, 2019
• Last Update Posted: April 18, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: April 12, 2019
• First Posted Date: April 16, 2019
• Last Update Posted Date: April 18, 2023
• Actual Study Start Date: June 4, 2019
• Actual Primary Completion Date: September 22, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 25, 2021): Objective Response Rate (ORR) as Determined by Independent Radiology Review (IRR) per RECIST v1.1 in the Treatment Naïve and Previously Treated Settings [ Time Frame: Up to 24 months ]
• Original Primary Outcome Measures (submitted: April 12, 2019): Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Up to 24 months ]

Current Secondary Outcome Measures (submitted: November 17, 2021)

• Duration of Response (DOR) as Determined by Independent Radiology Review (IRR) and Investigator [ Time Frame: Up to 24 months ]
• Disease Control Rate (DCR) as Determined by Independent Radiology Review (IRR) and Investigator [ Time Frame: Up to 24 months ]
• Progression-free Survival (PFS) as Determined by Independent Radiology Review (IRR) and Investigator [ Time Frame: Up to 24 months ]
• Overall Survival (OS) [ Time Frame: Up to 24 months ]
• Incidence and severity of adverse events (AEs) [ Time Frame: Up to 24 months ]
• Objective Response Rate (ORR) as determined by Investigator based on RECIST v1.1 [ Time Frame: Up to 24 Months ]
• Time to Tumor Response (TTR) as determined by Independent Radiology Review (IRR) and Investigator [ Time Frame: Up to 24 months ]

Original Secondary Outcome Measures (submitted: April 12, 2019)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
• Official Title: A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• Drug: encorafenib
  self-administered orally
• Drug: binimetinib
  self-administered orally

Study Arms

Experimental: Treatment Period

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)

Interventions:

• Drug: encorafenib
• Drug: binimetinib

• Publications *: Riely GJ, Ahn MJ, Felip E, Ramalingam SS, Smit EF, Tsao AS, Alcasid A, Usari T, Wissel PS, Wilner KD, Johnson BE. Encorafenib plus binimetinib in patients with BRAFV600-mutant non-small cell lung cancer: phase II PHAROS study design. Future Oncol. 2022 Mar;18(7):781-791. doi: 10.2217/fon-2021-1250. Epub 2021 Dec 17.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 5, 2022): 98
• Original Estimated Enrollment (submitted: April 12, 2019): 40
• Estimated Study Completion Date: June 30, 2024
• Actual Primary Completion Date: September 22, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, Korea, Republic of, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT03915951
• Other Study ID Numbers: ARRAY-818-202; C4221008 ( Other Identifier: Alias Study Number ); 2019-000417-37 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Array BioPharma
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Array BioPharma
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2023