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

A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: encorafenib; Drug: binimetinib

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • UO di Oftalmologia- Azienda Ospedaliero Universitaria Di Bologna
  • Bologna, Italy, 40138
    • UOC di Anatomia Patologica- Azienda Ospedaliero Universitaria Di Bo logna
  • Milan, Italy, 20132
    • Irccs Ospedale San Raffaele
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • Unita Operativa Radiologia
  • Napli
    • Napli, Napli, Italy, 80131
      • Clinica Oculistica II, 2° Policlinico Federico II
  • TO
    • Torino, TO, Italy, 10126
      • Dermatologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
  • Torino
    • Orbassano, Torino, Italy, 10043
      • S.S.D. Oncologia Polmonare
    • Orbassano, Torino, Italy, 10043
      • SCDU Radiodiagnostica e S.S. Medicina Nucleare
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
  • Amsterdam, Netherlands, 1091 AC
    • OLVG, locatie Oost; Ophthalmology department
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Groningen, Netherlands, 9713 GZ
    • Ophthalmology Department
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center - PPDS
• Spain
  • Badalona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08023
    • Hospital Quiron Salud Barcelona
  • Barcelona, Spain, 08022
    • CETIR Centro Medico Teknon
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Córdoba, Spain, 14004
    • Grupo Cardiologico Corpal (Hospital de la Cruz Roja)
  • Esplugues de Llobregat, Spain, 08950
    • CETIR
  • L'Hospitalet de Llobregat, Spain, 08907
    • lnstitut Catala d'Oncologia_L'Hospitalet
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Málaga, Spain, 29010
    • Centro Hospitalario Integral Privado (CHIP)
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Seville, Spain, 41009
    • CERCO
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Majadahonda
  • Málaga
    • Málaga, Málaga, Spain, 29010
      • Hospital Regional Universitario de Malaga - Hospital General
• United States
  • Arizona
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center Cancer Center
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center Ophthalmology
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology
    • Santa Monica, California, United States, 90403
      • UCLA Stein Eye Center Santa Monica (OPH)
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Cancer Specialist
    • Bonita Springs, Florida, United States, 34135
      • Florida Cancer Specialists
    • Brandon, Florida, United States, 33511
      • Florida Cancer Specialist
    • Cape Coral, Florida, United States, 33909
      • Florida Cancer Specialists
    • Clearwater, Florida, United States, 33761
      • Florida Cancer Specialist
    • Fleming Island, Florida, United States, 32003
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33905
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33908
      • Florida Cancer Specialists
    • Gainesville, Florida, United States, 32605
      • Florida Cancer Specialist
    • Largo, Florida, United States, 33770
      • Florida Cancer Specialists
    • Lecanto, Florida, United States, 34461
      • Florida Cancer Specialist
    • Naples, Florida, United States, 34102
      • Florida Cancer Specialists
    • Ocala, Florida, United States, 34474
      • Florida Cancer Specialist
    • Orange City, Florida, United States, 32763
      • Florida Cancer Specialist
    • Orlando, Florida, United States, 32806
      • Florida Cancer Specialist
    • Port Charlotte, Florida, United States, 33980
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34236
      • Florida Cancer Specialists
    • Spring Hill, Florida, United States, 34608
      • Florida Cancer Specialists
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialist
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists PAN - SCRI - PPDS
    • Tampa, Florida, United States, 33607
      • Florida Cancer Specialist
    • Tavares, Florida, United States, 32778
      • Florida Cancer Specialist
    • The Villages, Florida, United States, 32159
      • Florida Cancer Specialist
    • Trinity, Florida, United States, 34655
      • Florida Cancer Specialist
    • Venice, Florida, United States, 34285
      • Florida Cancer Specialists
    • Venice, Florida, United States, 34292
      • Florida Cancer Specialists
    • Winter Park, Florida, United States, 32792
      • Florida Cancer Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
    • Atlanta, Georgia, United States, 30308
      • Winship Cancer Institute @ Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30342
      • Winship Cancer Institute @ Emory Saint Joseph's Hospital
    • Johns Creek, Georgia, United States, 30097
      • Winship Cancer Institute @ Emory Johns Creek Hospital
  • Illinois
    • Shiloh, Illinois, United States, 62269
      • Siteman Cancer Center - Shiloh
    • Shiloh, Illinois, United States, 62269
      • Memorial Hospital
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • MidAmerica Division, Inc. c/o Menorah Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Wilmer Eye Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston Inc
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston (OCB)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center/East
    • Boston, Massachusetts, United States, 02115
      • Dana Farber / Partners Cancer Care
    • Newton, Massachusetts, United States, 02459
      • Dana-Farber Cancer Institute - Chestnut Hill
  • Missouri
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center - St Peters
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center - West County
    • Independence, Missouri, United States, 64057
      • MidAmerica Division, Inc. c/o Centerpoint Medical Center
    • Kansas City, Missouri, United States, 64132
      • MidAmerica Division, Inc., c/o Research Medical Center
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63129
      • Siteman Cancer Center - South County
    • St Louis, Missouri, United States, 63108
      • Siteman Cancer Center
    • St Louis, Missouri, United States, 63110
      • Saint Louis Children's Hospital
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Cancer Center Basking Ridge
    • Edison, New Jersey, United States, 08837
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Regional Cancer Care Associates, LLC
    • Paramus, New Jersey, United States, 07652
      • Metropolitan Eye Care
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - New York Presbyterian Hospital
    • New York, New York, United States, 10065
      • Weill Cornell Medical College - New York Presbyterian Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
    • New York, New York, United States, 10021
      • Weill Cornell Eye Associates
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University James Cancer Hospital
    • Columbus, Ohio, United States, 43221
      • Martha Morehouse Medical Plaza
    • Columbus, Ohio, United States, 43203
      • Ohio State CarePoint East
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Hospital
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center - Thoracic Oncology Clinic
    • Columbus, Ohio, United States, 43212
      • Ohio State Eye and Ear Institute
    • Columbus, Ohio, United States, 43212
      • Stefanie Spielman Comprehensive Breast Cancer
    • Columbus, Ohio, United States, 43203
      • The Ohio State University East Hospital
    • Gahanna, Ohio, United States, 43230
      • Ohio State CarePoint Gahanna
    • Lewis Center, Ohio, United States, 43035
      • Ohio State Outpatient Care Lewis Center
    • Westerville, Ohio, United States, 43081
      • The Ohio State University East Hospital Ohio State Outpatient Care New Albany
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Providence Cancer Institute Clackamas Clinic
    • Newberg, Oregon, United States, 97132
      • Providence Cancer Institute Newberg Clinic
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute, Franz Clinic
    • Portland, Oregon, United States, 97225
      • Providence Oncology and Hematology Care Clinic - Westside
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Hillman Cancer Center - Arnold Palmer - Mt View
    • Monroeville, Pennsylvania, United States, 15146
      • UPMC Hillman Cancer Center Monroeville
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC Hillman Cancer Center - Passavant (HOA)
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC Hillman Cancer Center - Passavant (OHA)
    • Pittsburgh, Pennsylvania, United States, 15243
      • UPMC Hillman Cancer Center - Upper St. Clair
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Eye Center, Eye and Ear Institute
    • York, Pennsylvania, United States, 17403
      • WellSpan Health
    • York, Pennsylvania, United States, 17402
      • Weaver Eye Associates
    • York, Pennsylvania, United States, 17403
      • WellSpan Oncology Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology, PLLC
    • Cleveland, Tennessee, United States, 37311
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Shelbyville, Tennessee, United States, 37160
      • Tennessee Oncology, PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77090
      • Millennium Research & Clinical Development
    • Houston, Texas, United States, 77008
      • Houston Eye Associates - Gramercy Location
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98104
      • Eye associates Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)	Drug: encorafenib; self-administered orally; Drug: binimetinib; self-administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)	Objective Response Rate (ORR) was defined as the percentage of participants who had achieved a confirmed best overall response (Complete Response [CR] or Partial Response [PR]) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes [recorded as target lesion] must have reduction in short axis to <10 mm) and complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size [<10 mm in short axis]). PR was defined by a 30% or more decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. ORR was calculated with the exact 2-sided Clopper-Pearson 95% CI.	From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment	ORR was defined as the percentage of participants who had achieved a confirmed best overall response (CR or PR) per RECIST version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes [recorded as target lesion] must have reduction in short axis to <10 mm) and the complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size [<10 mm in short axis]). PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. ORR according to derived investigator assessment was calculated with the exact 2-sided Clopper-Pearson 95% CI.	From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months)
Duration of Response (DoR) by IRR and Investigator Assessments	DoR, based on IRR and Investigator assessments was defined as the time from the date of the first documented confirmed response (CR or PR) (by IRR and by Investigator, respectively) to the earliest date of disease progression, as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1, or death due to any cause. If a participant with a CR or PR had neither progressed nor died at the time of the analysis cutoff or at the start of any new anticancer therapy, the participant was censored at the date of last adequate tumor assessment. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. DoR was calculated for participants who had achieved a confirmed overall response (CR or PR). The estimate of the DoR survival function was constructed using the Kaplan-Meier method.	From the date of the first confirmed documented response (CR or PR) to the earliest date of disease progression or death due to any cause (up to 36 months)
Disease Control Rate (DCR) by IRR and Investigator Assessments	DCR was defined as the percentage of participants who had achieved a confirmed overall response of CR, PR or stable disease (SD), as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1 after 24 weeks (≥168 days) from the date of first dose of study intervention. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. SD was assigned when neither sufficient shrinkage to qualify for CR or PR, nor sufficient increase to qualify for PD was observed, taking as reference the nadir. DCR was calculated along with the exact 2-sided Clopper-Pearson 95% CI.	After 24 Weeks (≥168 days) from the date of first dose of study intervention
Progression-free Survival (PFS) by IRR and Investigator Assessments	PFS was defined as the time from the date of first dose of study intervention to the earliest date of disease progression, as determined by IRR and Investigator review of radiographic disease assessments per RECIST version 1.1, or death due to any cause, whichever occurred first. PD was defined by a 20% or more increase in the SOD of target lesions relative to nadir (smallest SOD considering baseline and all assessments prior to the time point under evaluation), with a minimum absolute increase of 5 mm relative to nadir; PD was assigned if any non-target lesion was marked "unequivocal progression". If a participant had not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment. PFS (months) = [(date of event or censoring - date of first dose) +1]/30.4375. The survival distribution function for PFS was estimated using the Kaplan-Meier method.	From the date of first dose of study drug to the earliest date of disease progression, or death due to any cause (up to 36 months)
Time to Response (TTR) by IRR and Investigator Assessments	TTR based on IRR and Investigator assessments was defined, for participants with an objective response, as the time, in months, from the date of first dose to the first documentation of objective response (CR or PR) which was subsequently confirmed (by IRR and by Investigator, respectively). TTR was calculated for the subgroup of participants with a confirmed objective tumor response.	From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months)
Kaplan-Meier Estimates of Overall Survival (OS)	OS was defined as the time from the date of first dose of study intervention to the date of death due to any cause. If a death had not been observed by the date of the analysis cutoff, OS was censored at the date of last contact. The survival distribution function for OS was estimated using the Kaplan-Meier method.	The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAE was a treatment-emergent adverse event that occurred during the on-treatment period. The on-treatment period was defined as the time from the first dose date of study intervention to the last dose of study drug administration date (when both drugs were permanently discontinued) +30 days or the earliest date of subsequent anti-cancer drug therapy minus 1 day, whichever occurred first. Relatedness to study intervention was determined by the investigator. The investigator made an assessment of intensity for each AE reported during the study according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3 events = severe AEs; Grade 4 events = life-threatening consequences, urgent intervention indicated; Grade 5 events = death related to AEs.	From the time the participant provided informed consent, through and including a minimum of 30 calendar days, after the last administration of the study intervention, and the safety follow-up visit (30 days [±7 days] after the EOT visit) (up to 36 months)
Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Hematology Laboratory Test Values Based on CTCAE Grade	Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time. Grade 4 was not applicable for the parameters of anemia, hemoglobin increased, leukocytosis and lymphocyte count increased as Grade 4 was not defined for these 4 parameters per CTCAE version 4.03.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, End of Treatment (EOT) ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)
Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Chemistry Laboratory Test Values Based on CTCAE Grade	Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time. Grade 4 was not applicable for the parameters of hyperglycemia and hypoalbuminemia as Grade 4 was not defined for these 2 parameters per CTCAE version 4.03.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, EOT ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)
Number of Participants With Notable Abnormal Vital Signs	Vital sign measurements were taken before blood collection for laboratory tests or at least 30 minutes after blood collection for laboratory tests, and were measured per institutional standards. Vital sign assessments included temperature, pulse rate, respiratory rate, and blood pressure (assessed in a recumbent, semi recumbent, or sitting position). The criteria of notably abnormal vital signs are listed below: Systolic blood pressure (mmHg): high: ≥160 mmHg with increase from baseline of ≥20 mmHg; low: ≤90 mmHg with decrease from baseline of ≥20 mmHg. Diastolic blood pressure (mmHg): high: ≥100 mmHg with increase from baseline of ≥15 mmHg; low: ≤50 mmHg with decrease from baseline of ≥15 mmHg. Pulse rate (bpm): high: ≥120 bpm with increase from baseline of ≥15 bpm; low: ≤50 bpm with decrease from baseline of ≥15 bpm. Weight (kg): high: ≥10% increase from baseline; low: ≥20% decrease from baseline. Temperature (°C): high: ≥37.5 °C; low: ≤36 °C.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days of Subsequent Cycles, EOT ±3 Days, and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)
Number of Participants With Notable ECG (QTcF) Values	The QTcF increase from baseline >30/60 msec and new QTcF >450/480/500 msec were defined as clinically notable ECG criteria. Triplicate ECG measurements were obtained. For new abnormal post-baseline values, the table below presents the number of participants with both non-missing baseline and post-baseline values, and baseline values not meeting the criteria. For abnormal changes from baseline, the table below presents the number of participants with both non-missing baseline and post-baseline evaluations. Baseline was defined as the average of the machine-read triplicate ECG measurements taken pre-dose on Day 1. Change from baseline was post-baseline - baseline values.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)
Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade	Cardiac ejection fraction was assessed by transthoracic echocardiogram (ECHO) or multigated acquisition (MUGA). Participants who developed signs/symptoms of congestive heart failure (CHF) at any point during the study were required to have an evaluation of LVEF measurements by ECHO or MUGA and were monitored per institutional guidelines. Participants were considered as having a LVEF abnormality if the worst post-value was CTCAE Grade 2, 3 or 4 according to the following classification: Grade 0: Non-missing value below Grade 2. Grade 2: LVEF between 40% and 50%, inclusive, or absolute change from baseline between -10% and < -20%. Grade 3: LVEF between 20% and 39%, inclusive, or absolute change from baseline ≤ -20%. Grade 4: LVEF lower than 20%. Baseline was defined as the last available and valid assessment before or on the start date of study intervention.	Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General 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.
• Riely GJ, Ahn MJ, Clarke JM, Dagogo-Jack I, Esper R, Felip E, Gelsomino F, Goldman JW, Hussein M, Johnson M, Marrone KA, Morgensztern D, Nadal E, Negrao MV, Offin M, Provencio M, Ramalingam SS, Roof L, Sanborn RE, Smit EF, Tsao A, Usari T, Alcasid A, Wilner K, Tonkovyd S, Zhang X, Johnson BE. Updated Efficacy and Safety From the Phase 2 PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic NSCLC-A Brief Report. J Thorac Oncol. 2025 Oct;20(10):1538-1547. doi: 10.1016/j.jtho.2025.05.023. Epub 2025 Jun 4.
• Riely GJ, Smit EF, Ahn MJ, Felip E, Ramalingam SS, Tsao A, Johnson M, Gelsomino F, Esper R, Nadal E, Offin M, Provencio M, Clarke J, Hussain M, Otterson GA, Dagogo-Jack I, Goldman JW, Morgensztern D, Alcasid A, Usari T, Wissel P, Wilner K, Pathan N, Tonkovyd S, Johnson BE. Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. J Clin Oncol. 2023 Jul 20;41(21):3700-3711. doi: 10.1200/JCO.23.00774. Epub 2023 Jun 4.
• Johnson ML, Smit EF, Felip E, Ramalingam SS, Ahn MJ, Tsao A, Johnson BE, Offin M, Hussein M, Dagogo-Jack I, Goldman JW, Clarke JM, Negrao MV, Sanborn RE, Morgensztern D, Usari T, Wilner K, Alejandro L, Rifi N, Zhang X, Riely GJ. Updated Overall Survival Analysis From the Phase II PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer. J Clin Oncol. 2025 Dec 10;43(35):3706-3713. doi: 10.1200/JCO-25-02023. Epub 2025 Oct 19.
• Baik C, Cheng ML, Dietrich M, Gray JE, Karim NA. A Practical Review of Encorafenib and Binimetinib Therapy Management in Patients with BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer. Adv Ther. 2024 Jul;41(7):2586-2605. doi: 10.1007/s12325-024-02839-4. Epub 2024 May 2.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Actual): September 22, 2022
• Study Completion (Actual): October 3, 2025

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; lung cancer; cancer; non-small cell lung cancer; Immunotherapy; BRAF mutation; BRAF inhibitor; PDL1; Phase 2; BRAF V600E; Encorafenib; Binimetinib; non small cell lung cancer; Open Label; Metastatic NSCLC; V600; Stage IV NSCLC; Array; PD-LI; First line platinum based chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; encorafenib; binimetinib
• Other Study ID Numbers: ARRAY-818-202; 2024-515929-28-00 (Registry Identifier: CTIS (EU)); C4221008; PHAROS (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No