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AzTrials

Non-small Cell Lung CancerPhase 2NCT03915951

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

A Phase 2 study testing encorafenib and binimetinib in people with Non-small Cell Lung Cancer, run by Pfizer at 143 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
encorafenib and binimetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
143 sitesin 5 countries
Study dates
4 Jun 2019to 3 Oct 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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 locations and contacts

143 sites in 5 countries.

143 sites in 5 countries

United States112 sites

  • Florida Cancer Specialist

    Altamonte Springs, Florida, 32701

  • Winship Cancer Institute @ Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

  • Winship Cancer Institute @ Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Johns Hopkins Bayview Medical Center

    Baltimore, Maryland, 21224

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • The Johns Hopkins Wilmer Eye Institute

    Baltimore, Maryland, 21287

  • Memorial Sloan Kettering Cancer Center Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Florida Cancer Specialists

    Bonita Springs, Florida, 34135

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Ophthalmic Consultants of Boston (OCB)

    Boston, Massachusetts, 02114

  • Ophthalmic Consultants of Boston Inc

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber / Partners Cancer Care

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center/East

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Florida Cancer Specialist

    Brandon, Florida, 33511

  • Florida Cancer Specialists

    Cape Coral, Florida, 33909

  • Tennessee Oncology, PLLC

    Chattanooga, Tennessee, 37404

  • Siteman Cancer Center - St Peters

    City of Saint Peters, Missouri, 63376

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Florida Cancer Specialist

    Clearwater, Florida, 33761

  • Tennessee Oncology, PLLC

    Cleveland, Tennessee, 37311

  • Ohio State CarePoint East

    Columbus, Ohio, 43203

  • The Ohio State University East Hospital

    Columbus, Ohio, 43203

  • The Ohio State University Hospital

    Columbus, Ohio, 43210

  • The Ohio State University James Cancer Hospital

    Columbus, Ohio, 43210

  • The Ohio State University Medical Center - Thoracic Oncology Clinic

    Columbus, Ohio, 43210

  • Ohio State Eye and Ear Institute

    Columbus, Ohio, 43212

  • Stefanie Spielman Comprehensive Breast Cancer

    Columbus, Ohio, 43212

  • Martha Morehouse Medical Plaza

    Columbus, Ohio, 43221

  • Siteman Cancer Center - West County

    Creve Coeur, Missouri, 63141

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • Hackensack University Medical Center

    Edison, New Jersey, 08837

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Florida Cancer Specialists

    Fleming Island, Florida, 32003

  • Florida Cancer Specialists

    Fort Myers, Florida, 33901

  • Florida Cancer Specialists

    Fort Myers, Florida, 33905

  • Florida Cancer Specialists

    Fort Myers, Florida, 33908

  • Florida Cancer Specialists

    Fort Myers, Florida, 33916

  • Ohio State CarePoint Gahanna

    Gahanna, Ohio, 43230

  • Florida Cancer Specialist

    Gainesville, Florida, 32605

  • UPMC Hillman Cancer Center - Arnold Palmer - Mt View

    Greensburg, Pennsylvania, 15601

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Regional Cancer Care Associates, LLC

    Hackensack, New Jersey, 07601

  • Houston Eye Associates - Gramercy Location

    Houston, Texas, 77008

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Millennium Research & Clinical Development

    Houston, Texas, 77090

  • MidAmerica Division, Inc. c/o Centerpoint Medical Center

    Independence, Missouri, 64057

  • Winship Cancer Institute @ Emory Johns Creek Hospital

    Johns Creek, Georgia, 30097

  • MidAmerica Division, Inc., c/o Research Medical Center

    Kansas City, Missouri, 64132

  • Florida Cancer Specialists

    Largo, Florida, 33770

  • Florida Cancer Specialist

    Lecanto, Florida, 34461

  • Ohio State Outpatient Care Lewis Center

    Lewis Center, Ohio, 43035

  • UCLA Hematology/Oncology

    Los Angeles, California, 90095

  • UPMC Hillman Cancer Center Monroeville

    Monroeville, Pennsylvania, 15146

  • Florida Cancer Specialists

    Naples, Florida, 34102

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care

    New York, New York, 10021

  • Weill Cornell Eye Associates

    New York, New York, 10021

  • Weill Cornell Medical College - New York Presbyterian Hospital

    New York, New York, 10021

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Weill Cornell Medical College - New York Presbyterian Hospital

    New York, New York, 10065

  • Providence Cancer Institute Newberg Clinic

    Newberg, Oregon, 97132

  • Dana-Farber Cancer Institute - Chestnut Hill

    Newton, Massachusetts, 02459

  • Florida Cancer Specialist

    Ocala, Florida, 34474

  • Florida Cancer Specialist

    Orange City, Florida, 32763

  • Florida Cancer Specialist

    Orlando, Florida, 32806

  • MidAmerica Division, Inc. c/o Menorah Medical Center

    Overland Park, Kansas, 66209

  • Metropolitan Eye Care

    Paramus, New Jersey, 07652

  • UPMC Eye Center, Eye and Ear Institute

    Pittsburgh, Pennsylvania, 15213

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UPMC Hillman Cancer Center - Passavant (HOA)

    Pittsburgh, Pennsylvania, 15237

  • UPMC Hillman Cancer Center - Passavant (OHA)

    Pittsburgh, Pennsylvania, 15237

  • UPMC Hillman Cancer Center - Upper St. Clair

    Pittsburgh, Pennsylvania, 15243

  • Florida Cancer Specialists

    Port Charlotte, Florida, 33980

  • Providence Cancer Institute, Franz Clinic

    Portland, Oregon, 97213

  • Providence Oncology and Hematology Care Clinic - Westside

    Portland, Oregon, 97225

  • UCLA Stein Eye Center Santa Monica (OPH)

    Santa Monica, California, 90403

  • UCLA Hematology/Oncology

    Santa Monica, California, 90404

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Florida Cancer Specialists

    Sarasota, Florida, 34236

  • Eye associates Northwest

    Seattle, Washington, 98104

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Tennessee Oncology, PLLC

    Shelbyville, Tennessee, 37160

  • Memorial Hospital

    Shiloh, Illinois, 62269

  • Siteman Cancer Center - Shiloh

    Shiloh, Illinois, 62269

  • Florida Cancer Specialists

    Spring Hill, Florida, 34608

  • Siteman Cancer Center

    St Louis, Missouri, 63108

  • Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Saint Louis Children's Hospital

    St Louis, Missouri, 63110

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Washington University

    St Louis, Missouri, 63110

  • Siteman Cancer Center - South County

    St Louis, Missouri, 63129

  • Florida Cancer Specialist

    St. Petersburg, Florida, 33705

  • Florida Cancer Specialists PAN - SCRI - PPDS

    Tallahassee, Florida, 32308

  • Florida Cancer Specialist

    Tampa, Florida, 33607

  • Florida Cancer Specialist

    Tavares, Florida, 32778

  • Florida Cancer Specialist

    The Villages, Florida, 32159

  • Florida Cancer Specialist

    Trinity, Florida, 34655

  • Florida Cancer Specialists

    Venice, Florida, 34285

  • Florida Cancer Specialists

    Venice, Florida, 34292

  • The Ohio State University East Hospital Ohio State Outpatient Care New Albany

    Westerville, Ohio, 43081

  • Florida Cancer Specialists

    Winter Park, Florida, 32792

  • Weaver Eye Associates

    York, Pennsylvania, 17402

  • WellSpan Health

    York, Pennsylvania, 17403

  • WellSpan Oncology Research

    York, Pennsylvania, 17403

  • Yuma Regional Medical Center Cancer Center

    Yuma, Arizona, 85364

  • Yuma Regional Medical Center Ophthalmology

    Yuma, Arizona, 85364

  • Yuma Regional Medical Center

    Yuma, Arizona, 85364

Other trials in United States

Spain17 sites

  • Hospital Clinic de Barcelona

    Badalona, 08036

  • Hospital del Mar

    Barcelona, 08003

  • CETIR Centro Medico Teknon

    Barcelona, 08022

  • Hospital Quiron Salud Barcelona

    Barcelona, 08023

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Grupo Cardiologico Corpal (Hospital de la Cruz Roja)

    Córdoba, 14004

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Cetir

    Esplugues de Llobregat, 08950

  • lnstitut Catala d'Oncologia_L'Hospitalet

    L'Hospitalet de Llobregat, 08907

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Puerta de Hierro - Majadahonda

    Majadahonda, Madrid, 28222

  • Hospital Regional Universitario de Malaga - Hospital General

    Málaga, Málaga, 29010

  • Centro Hospitalario Integral Privado (CHIP)

    Málaga, 29010

  • CERCO

    Seville, 41009

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital Universitario Virgen Del Rocio

    Seville, 41013

Other trials in Spain

Italy9 sites

  • UO di Oftalmologia- Azienda Ospedaliero Universitaria Di Bologna

    Bologna, 40138

  • UOC di Anatomia Patologica- Azienda Ospedaliero Universitaria Di Bo logna

    Bologna, 40138

  • Unita Operativa Radiologia

    Milan, Lombardy, 20132

  • IRCCS Ospedale San Raffaele

    Milan, 20132

  • Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale

    Naples, 80131

  • Clinica Oculistica II, 2° Policlinico Federico II

    Napli, Napli, 80131

  • S.S.D. Oncologia Polmonare

    Orbassano, Torino, 10043

  • SCDU Radiodiagnostica e S.S. Medicina Nucleare

    Orbassano, Torino, 10043

  • Dermatologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino

    Torino, TO, 10126

Other trials in Italy

Netherlands4 sites

  • Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis

    Amsterdam, 1066 CX

  • OLVG, locatie Oost; Ophthalmology department

    Amsterdam, 1091 AC

  • Ophthalmology department

    Groningen, 9713 GZ

  • University Medical Center Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

South Korea1 site

  • Samsung Medical Center - PPDS

    Seoul, 06351

Other trials in South Korea

About this study

Official title: 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.

Being tested
encorafenib, binimetinib
Keywords
lung cancer, cancer, non-small cell lung cancer, non small cell lung cancer, NSCLC, Encorafenib, Binimetinib, Phase 2, Open Label, BRAF mutation, BRAF V600E, Array, Stage IV NSCLC, Metastatic NSCLC, PDL1, PD-LI, Immunotherapy, First line platinum based chemotherapy, BRAF inhibitor, V600
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • encorafenibDrug

    self-administered orally

  • binimetinibDrug

    self-administered orally

Study groups in NCT03915951
Study groupRoleWhat they receive
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)
Receives: Drug: encorafenib; Drug: binimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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.

    Measured: From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months)

  2. 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.

    Measured: 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)

  3. 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.

    Measured: After 24 Weeks (≥168 days) from the date of first dose of study intervention

  4. 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.

    Measured: 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)

  5. 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.

    Measured: From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months)

  6. 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.

    Measured: The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months)

  7. 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.

    Measured: 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)

  8. 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.

    Measured: 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)

  9. 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.

    Measured: 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)

  10. 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.

    Measured: 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)

  11. 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.

    Measured: Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

  12. 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.

    Measured: Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2019
  2. Study start4 Jun 2019
  3. Primary completion22 Sep 2022
  4. Study completion3 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03915951
Sponsor's protocol ID
ARRAY-818-202
Other IDs
C4221008; PHAROS, 2024-515929-28-00
Status last verified
Mar 2026
First submitted
12 Apr 2019
Last updated
24 Mar 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Johnson ML. Reply to: Treatment Switching and Subsequent Therapy Confound Overall Survival Estimates in PHAROS. J Clin Oncol. 2026 Jun 20;44(18):1748-1749. doi: 10.1200/JCO-26-00311. Epub 2026 Mar 31. No abstract available.

    PubMed 41915880

  • 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 Apr;22(8):873-885. doi: 10.1080/14796694.2026.2645982. Epub 2026 Mar 30.

    PubMed 41910021

  • 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.

    PubMed 41109959

  • 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.

    PubMed 40480428

  • 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.

    PubMed 38698170

  • 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.

    PubMed 37270692

  • 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.

    PubMed 34918546

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing encorafenib and binimetinib in people with Non-small Cell Lung Cancer, run by Pfizer at 143 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 143 sites in United States, Spain, Italy, Netherlands, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR) (time frame: From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03915951, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.

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