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| ID | Type | Description | Link |
|---|---|---|---|
| C4221008; PHAROS | Other Identifier | Alias Study Number | |
| 2024-515929-28-00 | Registry Identifier | CTIS (EU) |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Period | Experimental | 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:
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| encorafenib | Drug | self-administered orally |
| |
| binimetinib |
| 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) |
| 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. |
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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:
Adequate hepatic and renal function characterized by the following at screening:
Key Exclusion Criteria:
Patients who have documentation of any of the following:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yuma Regional Medical Center Cancer Center | Yuma | Arizona | 85364 | United States | ||
| Yuma Regional Medical Center Ophthalmology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42391424 | Derived | Riely GJ, Martini JF, Pantoja Galicia N, Tunquist B, Wilner K, Huang RSP, Guo C, Deng S, Meng W, Kiely J, Zhou L, Smith DL, Hartman M, Cui C, Rifi N, Johnson BE, Tsao AS. Clinical validation of tissue and liquid companion diagnostics for BRAF V600E detection in non-small cell lung cancers from the PHAROS study. Cancer Res Commun. 2026 Jul 1. doi: 10.1158/2767-9764.CRC-26-0102. Online ahead of print. | |
| 41915880 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment-Naive | Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 24, 2021 | Sep 18, 2023 |
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| Drug |
self-administered orally |
|
| 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) |
| 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 |
| Derived |
| 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. |
| 41910021 | Derived | 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. |
| 41109959 | Derived | 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. |
| 40480428 | Derived | 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. |
| 38698170 | Derived | 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. |
| 37270692 | Derived | 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. |
| 34918546 | Derived | 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. |
| Previously Treated |
Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Baseline analysis population included all participants taking at least 1 dose of study intervention.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Treatment-Naive | Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| BG001 | Previously Treated | Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Eastern Cooperation Oncology Group (ECOG) Performance Status | ECOG Performance Status Scoring: Grade 0: Fully active, able to carry on all predisease performance without restriction; Grade 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours; Grade 3: capable of only limited self-care; confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled; cannot carry on any self-care; totally confined to bed or chair; Grade 5: dead. | Count of Participants | Participants |
| |||||||||||||||
| Smoking Status | Smoking history was collected at Screening by the Investigator or qualified designee. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Analysis population included all participants who received at least 1 dose of study intervention. | Posted | Number | 95% Confidence Interval | Percentage of Participants | 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 | 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. | Analysis population included all participants who received at least 1 dose of study intervention. | Posted | Number | 95% Confidence Interval | Percentage of Participants | From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months) |
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| Secondary | 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. | Not Posted | Oct 2026 | 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) | Participants | |||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis population included all participants who received at least 1 dose of study intervention. | Posted | Number | 95% Confidence Interval | Percentage of Participants | After 24 Weeks (≥168 days) from the date of first dose of study intervention |
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| Secondary | 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. | Not Posted | Oct 2026 | 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) | Participants | |||||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis population included all participants who received at least 1 dose of study intervention and who had confirmed objective tumor response (CR or PR). Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | Median | Full Range | Months | From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months) |
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| Secondary | 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. | Not Posted | Oct 2026 | The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months) | Participants | |||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Analysis Set included all participants who received at least 1 dose of study intervention. | Posted | Count of Participants | Participants | 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) |
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| Secondary | 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. | Safety Analysis Set included all participants who received at least 1 dose of study intervention. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | Count of Participants | Participants | 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) |
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| Secondary | 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. | Safety Analysis Set included all participants who received at least 1 dose of study intervention. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | Count of Participants | Participants | 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) |
| |||||||||||||||||||||||||||||||
| Secondary | 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. | Analysis population included all participants who received at least 1 dose of study intervention and had baseline and post-baseline vital sign values. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | Count of Participants | Participants | 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) |
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| Secondary | 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. | Safety Analysis Set included all participants who received at least 1 dose of study intervention. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | Count of Participants | Participants | Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months) |
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| Secondary | 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. | Analysis Population included all participants who received at least 1 dose of study intervention and had both baseline and post-baseline LVEF values. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | Count of Participants | Participants | Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months) |
|
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)
Same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both serious and non-serious event during the study. Safety analysis set included all participants who received at least 1 dose of study intervention.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment-Naive | Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. | 5 | 59 | 25 | 59 | 59 | 59 |
| EG001 | Previously Treated | Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. | 7 | 39 | 17 | 39 | 38 | 39 |
| EG002 | Total | Sum of all participants in the Study C4221008 (ARRAY-818-202) | 12 | 98 | 42 | 98 | 97 | 98 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Supraventricular tachyarrhythmia | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Duodenal ulcer | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Small intestinal haemorrhage | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Ophthalmic herpes zoster | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pneumonia mycoplasmal | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hallucination, auditory | Psychiatric disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Haemothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Peripheral embolism | Vascular disorders | MedDRA version 25.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hair texture abnormal | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 25.0 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 26, 2022 | Sep 18, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D008175 | Lung Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000601108 | encorafenib |
| C581313 | binimetinib |
Not provided
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Grade 1 |
|
| Former Smoking |
|
| Never Smoking |
|
| OG001 |
| Previously Treated |
Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
|
|
|
|
|
|
| Previously Treated |
Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| OG002 | Total | Sum of all participants in the Study C4221008 (ARRAY-818-202) |
|
|
Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.
| OG002 | Total | Sum of all participants in the Study C4221008 (ARRAY-818-202) |
|
|
| OG002 | Total | Sum of all participants in the Study C4221008 (ARRAY-818-202) |
|
|
| OG001 | Previously Treated | Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| OG002 | Total | Sum of all participants in the Study C4221008 (ARRAY-818-202) |
|
|
Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| OG002 | Total | Sum of all participants in the Study C4221008 (ARRAY-818-202) |
|
|
| OG001 | Previously Treated | Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal. |
| OG002 | Total | Sum of all participants in the Study C4221008 (ARRAY-818-202) |
|
|