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
3 other identifiers
interventional
98
5 countries
143
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 nonsmall-cell-lung-cancer
Started Jun 2019
Longer than P75 for phase_2 nonsmall-cell-lung-cancer
143 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 12, 2019
CompletedFirst Posted
Study publicly available on registry
April 16, 2019
CompletedStudy Start
First participant enrolled
June 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 22, 2022
CompletedResults Posted
Study results publicly available
October 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2025
CompletedMarch 24, 2026
March 1, 2026
3.3 years
April 12, 2019
September 18, 2023
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (12)
Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment
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
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
After 24 Weeks (≥168 days) from the date of first dose of study intervention
Progression-free Survival (PFS) by IRR and Investigator Assessments
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
From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months)
- +7 more secondary outcomes
Study Arms (1)
Treatment Period
EXPERIMENTALStudy 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
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (143)
Yuma Regional Medical Center Cancer Center
Yuma, Arizona, 85364, United States
Yuma Regional Medical Center Ophthalmology
Yuma, Arizona, 85364, United States
Yuma Regional Medical Center
Yuma, Arizona, 85364, United States
UCLA Hematology/Oncology
Los Angeles, California, 90095, United States
UCLA Stein Eye Center Santa Monica (OPH)
Santa Monica, California, 90403, United States
UCLA Hematology/Oncology
Santa Monica, California, 90404, United States
Florida Cancer Specialist
Altamonte Springs, Florida, 32701, United States
Florida Cancer Specialists
Bonita Springs, Florida, 34135, United States
Florida Cancer Specialist
Brandon, Florida, 33511, United States
Florida Cancer Specialists
Cape Coral, Florida, 33909, United States
Florida Cancer Specialist
Clearwater, Florida, 33761, United States
Florida Cancer Specialists
Fleming Island, Florida, 32003, United States
Florida Cancer Specialists
Fort Myers, Florida, 33901, United States
Florida Cancer Specialists
Fort Myers, Florida, 33905, United States
Florida Cancer Specialists
Fort Myers, Florida, 33908, United States
Florida Cancer Specialists
Fort Myers, Florida, 33916, United States
Florida Cancer Specialist
Gainesville, Florida, 32605, United States
Florida Cancer Specialists
Largo, Florida, 33770, United States
Florida Cancer Specialist
Lecanto, Florida, 34461, United States
Florida Cancer Specialists
Naples, Florida, 34102, United States
Florida Cancer Specialist
Ocala, Florida, 34474, United States
Florida Cancer Specialist
Orange City, Florida, 32763, United States
Florida Cancer Specialist
Orlando, Florida, 32806, United States
Florida Cancer Specialists
Port Charlotte, Florida, 33980, United States
Florida Cancer Specialists
Sarasota, Florida, 34232, United States
Florida Cancer Specialists
Sarasota, Florida, 34236, United States
Florida Cancer Specialists
Spring Hill, Florida, 34608, United States
Florida Cancer Specialist
St. Petersburg, Florida, 33705, United States
Florida Cancer Specialists PAN - SCRI - PPDS
Tallahassee, Florida, 32308, United States
Florida Cancer Specialist
Tampa, Florida, 33607, United States
Florida Cancer Specialist
Tavares, Florida, 32778, United States
Florida Cancer Specialist
The Villages, Florida, 32159, United States
Florida Cancer Specialist
Trinity, Florida, 34655, United States
Florida Cancer Specialists
Venice, Florida, 34285, United States
Florida Cancer Specialists
Venice, Florida, 34292, United States
Florida Cancer Specialists
Winter Park, Florida, 32792, United States
Winship Cancer Institute @ Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
Winship Cancer Institute @ Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Winship Cancer Institute @ Emory Johns Creek Hospital
Johns Creek, Georgia, 30097, United States
Memorial Hospital
Shiloh, Illinois, 62269, United States
Siteman Cancer Center - Shiloh
Shiloh, Illinois, 62269, United States
MidAmerica Division, Inc. c/o Menorah Medical Center
Overland Park, Kansas, 66209, United States
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231, United States
The Johns Hopkins Wilmer Eye Institute
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Ophthalmic Consultants of Boston (OCB)
Boston, Massachusetts, 02114, United States
Ophthalmic Consultants of Boston Inc
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Dana Farber / Partners Cancer Care
Boston, Massachusetts, 02115, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center/East
Boston, Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute - Chestnut Hill
Newton, Massachusetts, 02459, United States
Siteman Cancer Center - St Peters
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141, United States
MidAmerica Division, Inc. c/o Centerpoint Medical Center
Independence, Missouri, 64057, United States
MidAmerica Division, Inc., c/o Research Medical Center
Kansas City, Missouri, 64132, United States
Siteman Cancer Center
St Louis, Missouri, 63108, United States
Barnes-Jewish Hospital
St Louis, Missouri, 63110, United States
Saint Louis Children's Hospital
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Washington University
St Louis, Missouri, 63110, United States
Siteman Cancer Center - South County
St Louis, Missouri, 63129, United States
Memorial Sloan Kettering Cancer Center Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Hackensack University Medical Center
Edison, New Jersey, 08837, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Regional Cancer Care Associates, LLC
Hackensack, New Jersey, 07601, United States
Metropolitan Eye Care
Paramus, New Jersey, 07652, United States
Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
New York, New York, 10021, United States
Weill Cornell Eye Associates
New York, New York, 10021, United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, 10021, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, 10065, United States
Duke Cancer Center
Durham, North Carolina, 27710, United States
Ohio State CarePoint East
Columbus, Ohio, 43203, United States
The Ohio State University East Hospital
Columbus, Ohio, 43203, United States
The Ohio State University Hospital
Columbus, Ohio, 43210, United States
The Ohio State University James Cancer Hospital
Columbus, Ohio, 43210, United States
The Ohio State University Medical Center - Thoracic Oncology Clinic
Columbus, Ohio, 43210, United States
Ohio State Eye and Ear Institute
Columbus, Ohio, 43212, United States
Stefanie Spielman Comprehensive Breast Cancer
Columbus, Ohio, 43212, United States
Martha Morehouse Medical Plaza
Columbus, Ohio, 43221, United States
Ohio State CarePoint Gahanna
Gahanna, Ohio, 43230, United States
Ohio State Outpatient Care Lewis Center
Lewis Center, Ohio, 43035, United States
The Ohio State University East Hospital Ohio State Outpatient Care New Albany
Westerville, Ohio, 43081, United States
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, 97015, United States
Providence Cancer Institute Newberg Clinic
Newberg, Oregon, 97132, United States
Providence Cancer Institute, Franz Clinic
Portland, Oregon, 97213, United States
Providence Oncology and Hematology Care Clinic - Westside
Portland, Oregon, 97225, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
UPMC Hillman Cancer Center - Arnold Palmer - Mt View
Greensburg, Pennsylvania, 15601, United States
UPMC Hillman Cancer Center Monroeville
Monroeville, Pennsylvania, 15146, United States
UPMC Eye Center, Eye and Ear Institute
Pittsburgh, Pennsylvania, 15213, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
UPMC Hillman Cancer Center - Passavant (HOA)
Pittsburgh, Pennsylvania, 15237, United States
UPMC Hillman Cancer Center - Passavant (OHA)
Pittsburgh, Pennsylvania, 15237, United States
UPMC Hillman Cancer Center - Upper St. Clair
Pittsburgh, Pennsylvania, 15243, United States
Weaver Eye Associates
York, Pennsylvania, 17402, United States
WellSpan Health
York, Pennsylvania, 17403, United States
WellSpan Oncology Research
York, Pennsylvania, 17403, United States
Tennessee Oncology, PLLC
Chattanooga, Tennessee, 37404, United States
Tennessee Oncology, PLLC
Cleveland, Tennessee, 37311, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
Tennessee Oncology, PLLC
Shelbyville, Tennessee, 37160, United States
Houston Eye Associates - Gramercy Location
Houston, Texas, 77008, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Millennium Research & Clinical Development
Houston, Texas, 77090, United States
Eye associates Northwest
Seattle, Washington, 98104, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Unita Operativa Radiologia
Milan, Lombardy, 20132, Italy
Clinica Oculistica II, 2° Policlinico Federico II
Napli, Napli, 80131, Italy
S.S.D. Oncologia Polmonare
Orbassano, Torino, 10043, Italy
SCDU Radiodiagnostica e S.S. Medicina Nucleare
Orbassano, Torino, 10043, Italy
Dermatologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Torino, TO, 10126, Italy
UO di Oftalmologia- Azienda Ospedaliero Universitaria Di Bologna
Bologna, 40138, Italy
UOC di Anatomia Patologica- Azienda Ospedaliero Universitaria Di Bo logna
Bologna, 40138, Italy
IRCCS Ospedale San Raffaele
Milan, 20132, Italy
Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
Naples, 80131, Italy
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
Amsterdam, 1066 CX, Netherlands
OLVG, locatie Oost; Ophthalmology department
Amsterdam, 1091 AC, Netherlands
Ophthalmology department
Groningen, 9713 GZ, Netherlands
University Medical Center Groningen
Groningen, 9713 GZ, Netherlands
Samsung Medical Center - PPDS
Seoul, 06351, South Korea
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, Madrid, 28222, Spain
Hospital Regional Universitario de Malaga - Hospital General
Málaga, Málaga, 29010, Spain
Hospital Clinic de Barcelona
Badalona, 08036, Spain
Hospital del Mar
Barcelona, 08003, Spain
CETIR Centro Medico Teknon
Barcelona, 08022, Spain
Hospital Quiron Salud Barcelona
Barcelona, 08023, Spain
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
Grupo Cardiologico Corpal (Hospital de la Cruz Roja)
Córdoba, 14004, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Cetir
Esplugues de Llobregat, 08950, Spain
lnstitut Catala d'Oncologia_L'Hospitalet
L'Hospitalet de Llobregat, 08907, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Hospitalario Integral Privado (CHIP)
Málaga, 29010, Spain
CERCO
Seville, 41009, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital Universitario Virgen Del Rocio
Seville, 41013, Spain
Related Publications (6)
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. A plain language summary of the updated results from the PHAROS study: the combination of encorafenib plus binimetinib for people with BRAF V600E-mutant metastatic non-small cell lung cancer. Future Oncol. 2026 Mar 30:1-13. doi: 10.1080/14796694.2026.2645982. Online ahead of print.
PMID: 41910021DERIVEDJohnson 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.
PMID: 41109959DERIVEDRiely 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.
PMID: 40480428DERIVEDBaik 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.
PMID: 38698170DERIVEDRiely 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.
PMID: 37270692DERIVEDRiely 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.
PMID: 34918546DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2019
First Posted
April 16, 2019
Study Start
June 4, 2019
Primary Completion
September 22, 2022
Study Completion
October 3, 2025
Last Updated
March 24, 2026
Results First Posted
October 30, 2023
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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.