History of Changes for Study: NCT03915951

Version	Submitted Date	Changes
1	April 12, 2019	None (earliest Version on record)
2	June 28, 2019	Recruitment Status, Study Status, Contacts/Locations and Oversight
3	September 30, 2019	Study Status and Contacts/Locations
4	November 5, 2019	Contacts/Locations and Study Status
5	June 25, 2020	Contacts/Locations, Study Identification, Sponsor/Collaborators, Study Status and IPDSharing
6	August 16, 2020	Contacts/Locations, Study Status, References and Study Identification
7	September 15, 2020	Contacts/Locations, Study Status, Oversight and Study Identification
8	November 4, 2020	Contacts/Locations, Study Status and Study Design
9	November 14, 2020	Contacts/Locations, Study Design and Study Status
10	February 7, 2021	Contacts/Locations, Study Status and Study Design
11	April 12, 2021	Contacts/Locations, Study Status and Study Identification
12	May 11, 2021	Contacts/Locations and Study Status
13	May 25, 2021	Contacts/Locations, Outcome Measures, Study Status and Study Identification
14	July 14, 2021	Contacts/Locations and Study Status
15	August 13, 2021	Study Status and Contacts/Locations
16	September 27, 2021	Study Status, Contacts/Locations and Oversight
17	November 17, 2021	Study Status, Eligibility, Outcome Measures and Conditions
18	December 10, 2021	Study Status and Contacts/Locations
19	January 11, 2022	Contacts/Locations and Study Status
20	February 25, 2022	Study Status and Contacts/Locations
21	April 18, 2022	Contacts/Locations, Study Status and Study Design
22	May 23, 2022	Study Status and Contacts/Locations
23	June 13, 2022	Recruitment Status, Study Status, Contacts/Locations and Study Design
24	August 12, 2022	Contacts/Locations and Study Status
25	October 5, 2022	Study Status, Contacts/Locations and Study Design
26	November 16, 2022	Contacts/Locations and Study Status
27	December 29, 2022	Study Status and Contacts/Locations
28	February 16, 2023	Study Status and Contacts/Locations
29	March 16, 2023	Study Status and Contacts/Locations
30	April 17, 2023	Study Status
31	July 10, 2023	Study Status and Contacts/Locations
32	September 18, 2023	Quality Control Review has not concluded Returned: October 10, 2023 Outcome Measures, Study Status, Document Section and Contacts/Locations
33	October 26, 2023	Study Status, Outcome Measures
34	March 20, 2024	Study Status and Contacts/Locations
35	April 12, 2024	Study Status and Contacts/Locations

Primary Outcome Measures:

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) ]

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.

Secondary Outcome Measures:

Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment
[ Time Frame: From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months) ]

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.

Duration of Response (DoR) by IRR and Investigator Assessments
[ Time Frame: 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) ]

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.

Disease Control Rate (DCR) by IRR and Investigator Assessments
[ Time Frame: After 24 Weeks (≥168 days) from the date of first dose of study intervention ]

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.

Progression-free Survival (PFS) by IRR and Investigator Assessments
[ Time Frame: 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) ]

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.

Time to Response (TTR) by IRR and Investigator Assessments
[ Time Frame: From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months) ]

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.

Kaplan-Meier Estimates of Overall Survival (OS)
[ Time Frame: The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months) ]

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.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
[ Time Frame: 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) ]

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.

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
[ Time Frame: 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) ]

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.

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
[ Time Frame: 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) ]

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.

10.

Number of Participants With Notable Abnormal Vital Signs
[ Time Frame: 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) ]

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.

11.

Number of Participants With Notable ECG (QTcF) Values
[ Time Frame: Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months) ]

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.

12.

Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade
[ Time Frame: Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months) ]

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.

Minimum Age:

18 Years

Maximum Age:

Sex:

All

Gender Based:

Accepts Healthy Volunteers:

Criteria:

Key Inclusion Criteria:

Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is currently Stage IV.
Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local laboratory assay or the presence of other BRAFV600 mutations other than V600E (i.e. K or D) will be considered
Patients who are either treatment-naïve (e.g., no prior systemic therapy for advanced/metastatic disease), OR who have received 1) first-line platinum-based chemotherapy OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1(PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy.
Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1.
Adequate bone marrow function characterized by the following at screening:
- absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
- Platelets ≥ 100 × 10⁹/L;
- Hemoglobin ≥ 8.5 g/dL (with or without blood transfusions).
Adequate hepatic and renal function characterized by the following at screening:
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases; Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m².

Key Exclusion Criteria:

Patients who have documentation of any of the following:
- epidermal growth factor receptor (EGFR) mutation
- anaplastic lymphoma kinase (ALK) fusion oncogene or
- ROS1 rearrangement
Patients who have received more than 1 prior line of systemic therapy in the advanced/metastatic setting.
Previous treatment with any BRAF inhibitor (e.g., dabrafenib, vemurafenib, XL281/BMS-908662, etc.), or any mitogen-activated protein kinase (MEK) inhibitor (e.g., trametinib, cobimetinib, selumetinib, RDEA119, etc.) prior to screening and enrollment.
Impaired cardiovascular function or clinically significant cardiovascular diseases
History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease.
Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phospho)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
Patients with symptomatic brain metastasis, leptomeningeal disease or other active central nervous system (CNS) metastases are not eligible.

Study Officials:

Pfizer CT.gov Call Center
Study Director
Pfizer

Locations:

United States, Arizona

Yuma Regional Medical Center Cancer Center
Yuma, Arizona, United States, 85364

Yuma Regional Medical Center Ophthalmology
Yuma, Arizona, United States, 85364

Yuma Regional Medical Center
Yuma, Arizona, United States, 85364

United States, California

UCLA Stein Eye Center Santa Monica (OPH)
Santa Monica, California, United States, 90403

UCLA Hematology/Oncology
Santa Monica, California, United States, 90404

United States, Florida

Florida Cancer Specialist
Altamonte Springs, Florida, United States, 32701

Florida Cancer Specialists
Bonita Springs, Florida, United States, 34135

Florida Cancer Specialist
Brandon, Florida, United States, 33511

Florida Cancer Specialists
Cape Coral, Florida, United States, 33909

Florida Cancer Specialist
Clearwater, Florida, United States, 33761

Florida Cancer Specialists
Fleming Island, Florida, United States, 32003

Florida Cancer Specialists
Fort Myers, Florida, United States, 33905

Florida Cancer Specialists
Fort Myers, Florida, United States, 33908

Florida Cancer Specialist
Gainesville, Florida, United States, 32605

Florida Cancer Specialists
Largo, Florida, United States, 33770

Florida Cancer Specialist
Lecanto, Florida, United States, 34461

Florida Cancer Specialists
Naples, Florida, United States, 34102

Florida Cancer Specialist
Ocala, Florida, United States, 34474

Florida Cancer Specialist
Orange City, Florida, United States, 32763

Florida Cancer Specialist
Orlando, Florida, United States, 32806

Florida Cancer Specialists
Port Charlotte, Florida, United States, 33980

Florida Cancer Specialist
Saint Petersburg, Florida, United States, 33705

Florida Cancer Specialists
Sarasota, Florida, United States, 34232

Florida Cancer Specialists
Sarasota, Florida, United States, 34236

Florida Cancer Specialists
Spring Hill, Florida, United States, 34608

Florida Cancer Specialists PAN - SCRI - PPDS
Tallahassee, Florida, United States, 32308

Florida Cancer Specialist
Tampa, Florida, United States, 33607

Florida Cancer Specialist
Tavares, Florida, United States, 32778

Florida Cancer Specialist
The Villages, Florida, United States, 32159

Florida Cancer Specialist
Trinity, Florida, United States, 34655

Florida Cancer Specialists
Venice, Florida, United States, 34285

Florida Cancer Specialists
Venice, Florida, United States, 34292

Florida Cancer Specialists
Winter Park, Florida, United States, 32792

United States, Georgia

Winship Cancer Institute @ Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308

Emory University Hospital
Atlanta, Georgia, United States, 30322

Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322

Winship Cancer Institute @ Emory Saint Joseph's Hospital
Atlanta, Georgia, United States, 30342

Winship Cancer Institute @ Emory Johns Creek Hospital
Johns Creek, Georgia, United States, 30097

United States, Kansas

MidAmerica Division, Inc. c/o Menorah Medical Center
Overland Park, Kansas, United States, 66209

United States, Maryland

Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287

The Johns Hopkins Wilmer Eye Institute
Baltimore, Maryland, United States, 21287

United States, Massachusetts

Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Ophthalmic Consultants of Boston (OCB)
Boston, Massachusetts, United States, 02114

Ophthalmic Consultants of Boston Inc
Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115

Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115

Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Beth Israel Deaconess Medical Center - 330 Brookline Ave
Boston, Massachusetts, United States, 02215-5400

Beth Israel Deaconess Medical Center/East
Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute - Chestnut Hill
Newton, Massachusetts, United States, 02459

United States, Missouri

Siteman Cancer Center - West County
Creve Coeur, Missouri, United States, 63141

MidAmerica Division, Inc. c/o Centerpoint Medical Center
Independence, Missouri, United States, 64057

MidAmerica Division, Inc., c/o Research Medical Center
Kansas City, Missouri, United States, 64132

Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110

Washington University School of Medicine
Saint Louis, Missouri, United States, 63110

Siteman Cancer Center - South County
Saint Louis, Missouri, United States, 63129

Siteman Cancer Center - St Peters
Saint Peters, Missouri, United States, 63376

United States, New Jersey

Memorial Sloan Kettering Cancer Center Basking Ridge
Basking Ridge, New Jersey, United States, 07920

Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601

Metropolitan Eye Care
Paramus, New Jersey, United States, 07652

United States, New York

Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
New York, New York, United States, 10021

Weill Cornell Eye Associates
New York, New York, United States, 10021

Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, United States, 10021

Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065

Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, United States, 10065

United States, North Carolina

Duke Cancer Center
Durham, North Carolina, United States, 27710

United States, Ohio

Ohio State CarePoint East
Columbus, Ohio, United States, 43203

The Ohio State University Hospital
Columbus, Ohio, United States, 43210

The Ohio State University James Cancer Hospital
Columbus, Ohio, United States, 43210

The Ohio State University Medical Center - Thoracic Oncology Clinic
Columbus, Ohio, United States, 43210

Ohio State Eye and Ear Institute
Columbus, Ohio, United States, 43212

Stefanie Spielman Comprehensive Breast Cancer
Columbus, Ohio, United States, 43212

Martha Morehouse Medical Plaza
Columbus, Ohio, United States, 43221

Ohio State CarePoint Gahanna
Gahanna, Ohio, United States, 43230

Ohio State Outpatient Care Lewis Center
Lewis Center, Ohio, United States, 43035

United States, Oregon

Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, United States, 97015

Providence Cancer Institute Newberg Clinic
Newberg, Oregon, United States, 97132

Providence Cancer Institute, Franz Clinic
Portland, Oregon, United States, 97213

Providence Oncology and Hematology Care Clinic - Westside
Portland, Oregon, United States, 97225

United States, Pennsylvania

UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, United States, 16505

UPMC Hillman Cancer Center - Arnold Palmer - Mt View
Greensburg, Pennsylvania, United States, 15601

UPMC Hillman Cancer Center Monroeville
Monroeville, Pennsylvania, United States, 15146

UPMC Eye Center, Eye and Ear Institute
Pittsburgh, Pennsylvania, United States, 15213-2548

UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232

UPMC Hillman Cancer Center - Passavant (HOA)
Pittsburgh, Pennsylvania, United States, 15237

UPMC Hillman Cancer Center - Passavant (OHA)
Pittsburgh, Pennsylvania, United States, 15237

UPMC Hillman Cancer Center - Upper St. Clair
Pittsburgh, Pennsylvania, United States, 15243

Weaver Eye Associates
York, Pennsylvania, United States, 17402

WellSpan Oncology Research
York, Pennsylvania, United States, 17403

United States, Tennessee

Tennessee Oncology, PLLC
Chattanooga, Tennessee, United States, 37404

Tennessee Oncology, PLLC
Cleveland, Tennessee, United States, 37311

Tennessee Oncology, PLLC
Dickson, Tennessee, United States, 37055

Tennessee Oncology, PLLC
Franklin, Tennessee, United States, 37067

Tennessee Oncology, PLLC
Gallatin, Tennessee, United States, 37066

Tennessee Oncology, PLLC
Hendersonville, Tennessee, United States, 37075

Tennessee Oncology, PLLC
Hermitage, Tennessee, United States, 37076

Tennessee Oncology, PLLC
Lebanon, Tennessee, United States, 37090

Tennessee Oncology, PLLC
Murfreesboro, Tennessee, United States, 37129

Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203

Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37205

Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37207

Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37211

Tennessee Oncology, PLLC
Shelbyville, Tennessee, United States, 37160

Tennessee Oncology, PLLC
Smyrna, Tennessee, United States, 37167

United States, Texas

Houston Eye Associates - Gramercy Location
Houston, Texas, United States, 77008

The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009

Millennium Research & Clinical Development
Houston, Texas, United States, 77090-3063

United States, Washington

Eye associates Northwest
Seattle, Washington, United States, 98104

Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109

Italy

UO Dermatologia Centro Tumori Cutanei (CTC)- Azienda Ospedaliero
Bologna, Italy, 40138

UO di Oftalmologia- Azienda Ospedaliero Universitaria Di Bologna
Bologna, Italy, 40138

UO Farmacia Clinica- Azienda Ospedaliero Universitaria Di Bologna
Bologna, Italy, 40138

UO Medicina Borghi- Azienda Ospedaliero Universitaria Di Bologna
Bologna, Italy, 40138

UO Radiologia Golfieri- Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
Bologna, Italy, 40138

UOC di Anatomia Patologica- Azienda Ospedaliero Universitaria Di Bo logna
Bologna, Italy, 40138

IRCCS Ospedale San Raffaele
Milan, Italy, 20132

Clinica Oculistica II, 2° Policlinico Federico II
Napli, Italy, 80131

S. C. Farmacia
Napoli, Italy, 80131

Italy, Lombardia

Departimento Oncologia Medica
Milan, Lombardia, Italy, 20132

Unita Operativa di Oculistica: UO Oncologia Oculare e Immunopatologia oculare
Milan, Lombardia, Italy, 20132

Unita Operativa Radiologia
Milan, Lombardia, Italy, 20132

UO Anatomia e lstologia Patologica
Milan, Lombardia, Italy, 20132

UO Dermatologia e Cosmetologia
Milan, Lombardia, Italy, 20132

UO Medicina Nucleare
Milan, Lombardia, Italy, 20132

UOC Farmacia
Milan, Lombardia, Italy, 20132

Italy, TO

Dermatologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Torino, TO, Italy, 10126

Italy, Torino

S.S.D. Oncologia Polmonare
Orbassano, Torino, Italy, 10043

SCDO Cardiologia
Orbassano, Torino, Italy, 10043

SCDU Anatomia Patologica
Orbassano, Torino, Italy, 10043

SCDU Oftalmologia
Orbassano, Torino, Italy, 10043

SCDU Radiodiagnostica e S.S. Medicina Nucleare
Orbassano, Torino, Italy, 10043

Korea, Republic of

Samsung Medical Center - PPDS
Seoul, Korea, Republic of, 06351

Samsung Medical Center
Seoul, Korea, Republic of, 06351

Netherlands

Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
Amsterdam, Netherlands, 1066 CX

OLVG, locatie Oost; Ophthalmology department
Amsterdam, Netherlands, 1091 AC

Ophthalmology department
Groningen, Netherlands, 9713 GZ

University Medical Center Groningen
Groningen, Netherlands, 9713 GZ

Netherlands, Noord-holland

Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
Amsterdam, Noord-holland, Netherlands, 1066 CX

Spain

Hospital Clinic de Barcelona
Badalona, Spain, 08036

Hospital del Mar
Barcelona, Spain, 08003

CETIR Centro Medico Teknon
Barcelona, Spain, 08022

Hospital Quiron Salud Barcelona
Barcelona, Spain, 08023

Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035

Grupo Cardiologico Corpal (Hospital de la Cruz Roja)
Cordoba, Spain, 14004

Hospital Universitario Reina Sofia
Cordoba, Spain, 14004

Cetir
Esplugues de Llobregat, Spain, 08950

lnstitut Catala d'Oncologia_L'Hospitalet
L'Hospitalet, Spain, 08907

Hospital Universitario Ramon y Cajal
Madrid, Spain, 28034

Hospital Universitario 12 de Octubre
Madrid, Spain, 28041

Centro Hospitalario Integral Privado (CHIP)
Malaga, Spain, 29010

CERCO
Sevilla, Spain, 41009

Hospital Universitario Virgen Macarena
Sevilla, Spain, 41009

Hospital Universitario Virgen Del Rocio
Sevilla, Spain, 41013

Spain, Madrid

Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, Madrid, Spain, 28222

Spain, Málaga

Hospital Regional Universitario de Malaga - Hospital General
Malaga, Málaga, Spain, 29010

Arm/Group Title

Treatment-Naive

Previously Treated

Arm/Group Description

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.

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.

Period Title: Overall Study

Started

Completed

Not Completed

Reason Not Completed

As of the PCD data-cut, 33 participants remained on-treatment.

Adverse Event

Disease progression (radiological)

Disease progression (clinical)

Patient decision

Investigator decision

Consent withdrawn

Death

Outcome Measures

1. Primary Outcome:

Title

Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)

Description

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.

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)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention.


Arm/Group Title	Treatment-Naive	Previously Treated
Arm/Group Description	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.	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.
Overall Number of Participants Analyzed	59	39
Number (95% Confidence Interval) Unit of Measure: Percentage of Participants	74.6(61.6 to 85.0)	46.2(30.1 to 62.8)

2. Secondary Outcome:

Title

Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment

Description

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.

Time Frame

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

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention.


Arm/Group Title	Treatment-Naive	Previously Treated
Arm/Group Description	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.	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.
Overall Number of Participants Analyzed	59	39
Number (95% Confidence Interval) Unit of Measure: Percentage of Participants	62.7(49.1 to 75.0)	41.0(25.6 to 57.9)

3. Secondary Outcome:


Title	Duration of Response (DoR) by IRR and Investigator Assessments
Description	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.
Time Frame	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)
Anticipated Reporting Date	June 2025
Outcome Measure Data Not Reported

4. Secondary Outcome:

Title

Disease Control Rate (DCR) by IRR and Investigator Assessments

Description

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.

Time Frame

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

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention.


Arm/Group Title	Treatment-Naive	Previously Treated
Arm/Group Description	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.	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.
Overall Number of Participants Analyzed	59	39
Number (95% Confidence Interval) Unit of Measure: Percentage of Participants
DCR After 24 Weeks by IRR	64.4(50.9 to 76.4)	41.0(25.6 to 57.9)
DCR After 24 Weeks by Investigator Assessment	67.8(54.4 to 79.4)	48.7(32.4 to 65.2)

5. Secondary Outcome:


Title	Progression-free Survival (PFS) by IRR and Investigator Assessments
Description	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.
Time Frame	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)
Anticipated Reporting Date	June 2025
Outcome Measure Data Not Reported

6. Secondary Outcome:

Title

Time to Response (TTR) by IRR and Investigator Assessments

Description

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.

Time Frame

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

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title		Treatment-Naive	Previously Treated
Arm/Group Description		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.	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.
Overall Number of Participants Analyzed		59	39
Median (Full Range) Unit of Measure: Months
TTR by IRR	Number Analyzed	Participants	Participants
TTR by IRR		1.86(1.1 to 19.1)	1.74(1.2 to 7.3)
TTR by Investigator Assessment	Number Analyzed	Participants	Participants
TTR by Investigator Assessment		1.84(1.4 to 14.0)	1.81(0.8 to 9.2)

7. Secondary Outcome:


Title	Kaplan-Meier Estimates of Overall Survival (OS)
Description	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.
Time Frame	The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months)
Anticipated Reporting Date	June 2025
Outcome Measure Data Not Reported

8. Secondary Outcome:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Description

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.

Time Frame

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)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all participants who received at least 1 dose of study intervention.


Arm/Group Title	Treatment-Naive	Previously Treated	Total
Arm/Group Description	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.	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.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed	59	39	98
Measure Type: Count of Participants Unit of Measure: Participants
Participants With TEAEs	59 100%	38 97.4%	97 99%
Participants With Treatment-related TEAEs	58 98.3%	34 87.2%	92 93.9%
Participants with Maximum Grade 3 or 4 TEAEs	37 62.7%	18 46.2%	55 56.1%
Participants with Maximum Treatment-related Grade 3 or 4 TEAEs	27 45.8%	13 33.3%	40 40.8%
Participants With Grade 5 TEAEs	5 8.5%	7 17.9%	12 12.2%
Participants With Treatment-related Grade 5 TEAEs	1 1.7%	0 0%	1 1%

9. Secondary Outcome:

Title

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

Description

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.

Time Frame

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)

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description		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.	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.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants Unit of Measure: Participants
Anemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Anemia - Grade 3		9 15.3%	1 2.6%	10 10.2%
Anemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Anemia - Grade 4		NA^[1]	NA^[1]	NA^[1]
Hemoglobin increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Hemoglobin increased - Grade 3		0 0%	0 0%	0 0%
Hemoglobin increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Hemoglobin increased - Grade 4		NA^[1]	NA^[1]	NA^[1]
Leukocytosis - Grade 3	Number Analyzed	Participants	Participants	Participants
Leukocytosis - Grade 3		0 0%	0 0%	0 0%
Leukocytosis - Grade 4	Number Analyzed	Participants	Participants	Participants
Leukocytosis - Grade 4		NA^[1]	NA^[1]	NA^[1]
Lymphocyte count decreased - Grade 3	Number Analyzed	Participants	Participants	Participants
Lymphocyte count decreased - Grade 3		2 3.4%	3 7.7%	5 5.1%
Lymphocyte count decreased - Grade 4	Number Analyzed	Participants	Participants	Participants
Lymphocyte count decreased - Grade 4		0 0%	0 0%	0 0%
Lymphocyte count increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Lymphocyte count increased - Grade 3		0 0%	0 0%	0 0%
Lymphocyte count increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Lymphocyte count increased - Grade 4		NA^[1]	NA^[1]	NA^[1]
Neutrophil count decreased - Grade 3	Number Analyzed	Participants	Participants	Participants
Neutrophil count decreased - Grade 3		1 1.7%	0 0%	1 1%
Neutrophil count decreased - Grade 4	Number Analyzed	Participants	Participants	Participants
Neutrophil count decreased - Grade 4		0 0%	0 0%	0 0%
Platelet count decreased - Grade 3	Number Analyzed	Participants	Participants	Participants
Platelet count decreased - Grade 3		0 0%	1 2.6%	1 1%
Platelet count decreased - Grade 4	Number Analyzed	Participants	Participants	Participants
Platelet count decreased - Grade 4		0 0%	0 0%	0 0%
White blood cell decreased - Grade 3	Number Analyzed	Participants	Participants	Participants
White blood cell decreased - Grade 3		0 0%	0 0%	0 0%
White blood cell decreased - Grade 4	Number Analyzed	Participants	Participants	Participants
White blood cell decreased - Grade 4		0 0%	0 0%	0 0%

[1]	NA Explanation: CTCAE Grade 4 was not defined for this parameter.

Quality Control Review Comment provided by the National Library of Medicine:

The explanation provided is not sufficient to understand why one or more values are not available.

10. Secondary Outcome:

Title

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

Description

Time Frame

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)

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description		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.	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.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants Unit of Measure: Participants
Alanine aminotransferase increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Alanine aminotransferase increased - Grade 3		6 10.2%	2 5.1%	8 8.2%
Alanine aminotransferase increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Alanine aminotransferase increased - Grade 4		0 0%	0 0%	0 0%
Alkaline phosphatase increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Alkaline phosphatase increased - Grade 3		2 3.4%	1 2.6%	3 3.1%
Alkaline phosphatase increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Alkaline phosphatase increased - Grade 4		0 0%	0 0%	0 0%
Aspartate aminotransferase increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Aspartate aminotransferase increased - Grade 3		7 11.9%	2 5.1%	9 9.2%
Aspartate aminotransferase increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Aspartate aminotransferase increased - Grade 4		0 0%	0 0%	0 0%
Blood bilirubin increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Blood bilirubin increased - Grade 3		0 0%	0 0%	0 0%
Blood bilirubin increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Blood bilirubin increased - Grade 4		0 0%	0 0%	0 0%
Creatine kinase increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Creatine kinase increased - Grade 3		2 3.4%	1 2.6%	3 3.1%
Creatine kinase increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Creatine kinase increased - Grade 4		0 0%	0 0%	0 0%
Creatinine increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Creatinine increased - Grade 3		3 5.1%	0 0%	3 3.1%
Creatinine increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Creatinine increased - Grade 4		0 0%	0 0%	0 0%
Hypercalcemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypercalcemia - Grade 3		1 1.7%	1 2.6%	2 2%
Hypercalcemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypercalcemia - Grade 4		0 0%	0 0%	0 0%
Hyperglycemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hyperglycemia - Grade 3		5 8.5%	1 2.6%	6 6.1%
Hyperglycemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hyperglycemia - Grade 4		NA^[1]	NA^[1]	NA^[1]
Hyperkalemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hyperkalemia - Grade 3		2 3.4%	0 0%	2 2%
Hyperkalemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hyperkalemia - Grade 4		0 0%	0 0%	0 0%
Hypermagnesemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypermagnesemia - Grade 3		0 0%	1 2.6%	1 1%
Hypermagnesemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypermagnesemia - Grade 4		0 0%	0 0%	0 0%
Hypernatremia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypernatremia - Grade 3		0 0%	0 0%	0 0%
Hypernatremia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypernatremia - Grade 4		0 0%	0 0%	0 0%
Hypoalbuminemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypoalbuminemia - Grade 3		0 0%	0 0%	0 0%
Hypoalbuminemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypoalbuminemia - Grade 4		NA^[1]	NA^[1]	NA^[1]
Hypocalcemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypocalcemia - Grade 3		0 0%	0 0%	0 0%
Hypocalcemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypocalcemia - Grade 4		2 3.4%	0 0%	2 2%
Hypoglycemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypoglycemia - Grade 3		0 0%	0 0%	0 0%
Hypoglycemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypoglycemia - Grade 4		0 0%	0 0%	0 0%
Hypokalemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypokalemia - Grade 3		0 0%	1 2.6%	1 1%
Hypokalemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypokalemia - Grade 4		0 0%	0 0%	0 0%
Hypomagnesemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypomagnesemia - Grade 3		0 0%	0 0%	0 0%
Hypomagnesemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypomagnesemia - Grade 4		0 0%	0 0%	0 0%
Hyponatremia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hyponatremia - Grade 3		7 11.9%	2 5.1%	9 9.2%
Hyponatremia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hyponatremia - Grade 4		0 0%	0 0%	0 0%
Hypophosphatemia - Grade 3	Number Analyzed	Participants	Participants	Participants
Hypophosphatemia - Grade 3		1 1.7%	0 0%	1 1%
Hypophosphatemia - Grade 4	Number Analyzed	Participants	Participants	Participants
Hypophosphatemia - Grade 4		0 0%	0 0%	0 0%
Lipase increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Lipase increased - Grade 3		8 13.6%	3 7.7%	11 11.2%
Lipase increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Lipase increased - Grade 4		2 3.4%	0 0%	2 2%
Serum amylase increased - Grade 3	Number Analyzed	Participants	Participants	Participants
Serum amylase increased - Grade 3		1 1.7%	0 0%	1 1%
Serum amylase increased - Grade 4	Number Analyzed	Participants	Participants	Participants
Serum amylase increased - Grade 4		0 0%	0 0%	0 0%

[1]	NA Explanation: CTCAE Grade 4 was not defined for this parameter.

Quality Control Review Comment provided by the National Library of Medicine:

The explanation provided is not sufficient to understand why one or more values are not available.

11. Secondary Outcome:

Title

Number of Participants With Notable Abnormal Vital Signs

Description

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.

Time Frame

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)

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description		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.	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.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants Unit of Measure: Participants
Systolic blood pressure - high	Number Analyzed	Participants	Participants	Participants
Systolic blood pressure - high		10 16.9%	4 10.3%	14 14.3%
Systolic blood pressure - low	Number Analyzed	Participants	Participants	Participants
Systolic blood pressure - low		5 8.5%	2 5.1%	7 7.1%
Diastolic blood pressure - high	Number Analyzed	Participants	Participants	Participants
Diastolic blood pressure - high		5 8.5%	1 2.6%	6 6.1%
Diastolic blood pressure - low	Number Analyzed	Participants	Participants	Participants
Diastolic blood pressure - low		2 3.4%	2 5.1%	4 4.1%
Pulse rate - high	Number Analyzed	Participants	Participants	Participants
Pulse rate - high		2 3.4%	6 15.4%	8 8.2%
Pulse rate - low	Number Analyzed	Participants	Participants	Participants
Pulse rate - low		1 1.7%	1 2.6%	2 2%
Weight - high	Number Analyzed	Participants	Participants	Participants
Weight - high		17 28.8%	4 10.3%	21 21.4%
Weight - low	Number Analyzed	Participants	Participants	Participants
Weight - low		1 1.7%	0 0%	1 1%
Temperature - high	Number Analyzed	Participants	Participants	Participants
Temperature - high		8 13.6%	3 7.7%	11 11.2%
Temperature - low	Number Analyzed	Participants	Participants	Participants
Temperature - low		25 42.4%	10 25.6%	35 35.7%

12. Secondary Outcome:

Title

Number of Participants With Notable ECG (QTcF) Values

Description

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.

Time Frame

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

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description		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.	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.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants Unit of Measure: Participants
New QTcF >450 msec	Number Analyzed	Participants	Participants	Participants
New QTcF >450 msec		12 20.3%	7 17.9%	19 19.4%
New QTcF >480 msec	Number Analyzed	Participants	Participants	Participants
New QTcF >480 msec		5 8.5%	5 12.8%	10 10.2%
New QTcF >500 msec	Number Analyzed	Participants	Participants	Participants
New QTcF >500 msec		1 1.7%	1 2.6%	2 2%
QTcF Increase from baseline >30 msec	Number Analyzed	Participants	Participants	Participants
QTcF Increase from baseline >30 msec		20 33.9%	9 23.1%	29 29.6%
QTcF Increase from baseline >60 msec	Number Analyzed	Participants	Participants	Participants
QTcF Increase from baseline >60 msec		3 5.1%	4 10.3%	7 7.1%

13. Secondary Outcome:

Title

Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade

Description

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.

Time Frame

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

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Treatment-Naive	Previously Treated	Total
Arm/Group Description	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.	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.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed	56	33	89
Measure Type: Count of Participants Unit of Measure: Participants
Grade 0	45 80.4%	24 72.7%	69 77.5%
Grade 2	11 19.6%	7 21.2%	18 20.2%
Grade 3	0 0%	2 6.1%	2 2.2%
Grade 4	0 0%	0 0%	0 0%

Time Frame

Adverse Event Reporting Description

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.

Arm/Group Title

Treatment-Naive

Previously Treated

Total

Arm/Group Description

Sum of all participants in the Study C4221008 (ARRAY-818-202)

All-Cause Mortality

Treatment-Naive

Previously Treated

Total

Affected / At Risk (%)

Total

5 / 59 (8.47%)

7 / 39 (17.95%)

12 / 98 (12.24%)

Serious Adverse Events

Treatment-Naive

Previously Treated

Total

Affected / At Risk (%)

Total

25 / 59 (42.37%)

17 / 39 (43.59%)

42 / 98 (42.86%)

Blood and lymphatic system disorders

Anaemia ^{∗ A}

3 / 59 (5.08%)

0 / 39 (0%)

3 / 98 (3.06%)

Disseminated intravascular coagulation ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Cardiac disorders

Atrial fibrillation ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Myocardial infarction ^{∗ A}

1 / 59 (1.69%)

1 / 39 (2.56%)

2 / 98 (2.04%)

Pericardial effusion ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Supraventricular tachyarrhythmia ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Tachycardia ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Eye disorders

Retinal detachment ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Gastrointestinal disorders

Colitis ^{∗ A}

4 / 59 (6.78%)

0 / 39 (0%)

4 / 98 (4.08%)

Constipation ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Diarrhoea ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Duodenal ulcer ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Gastrointestinal haemorrhage ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Nausea ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Small intestinal haemorrhage ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Upper gastrointestinal haemorrhage ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

General disorders

Asthenia ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Disease progression ^{∗ A}

2 / 59 (3.39%)

4 / 39 (10.26%)

6 / 98 (6.12%)

Oedema peripheral ^{∗ A}

2 / 59 (3.39%)

0 / 39 (0%)

2 / 98 (2.04%)

Hepatobiliary disorders

Cholecystitis ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Cholelithiasis ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Infections and infestations

COVID-19 ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

COVID-19 pneumonia ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Cellulitis ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Clostridium difficile colitis ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Device related infection ^{∗ A}

1 / 59 (1.69%)

1 / 39 (2.56%)

2 / 98 (2.04%)

Empyema ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Herpes zoster ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Ophthalmic herpes zoster ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Pneumonia ^{∗ A}

2 / 59 (3.39%)

0 / 39 (0%)

2 / 98 (2.04%)

Pneumonia mycoplasmal ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Respiratory tract infection ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Urinary tract infection ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Urosepsis ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Injury, poisoning and procedural complications

Femur fracture ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Head injury ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Hip fracture ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Upper limb fracture ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Investigations

Blood creatinine increased ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Metabolism and nutrition disorders

Hyponatraemia ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Musculoskeletal and connective tissue disorders

Back pain ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm progression ^{∗ A}

2 / 59 (3.39%)

2 / 39 (5.13%)

4 / 98 (4.08%)

Squamous cell carcinoma of skin ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Nervous system disorders

Cerebrovascular accident ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Cognitive disorder ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Haemorrhage intracranial ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Hemiparesis ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Presyncope ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Seizure ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Psychiatric disorders

Confusional state ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Hallucination, auditory ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Renal and urinary disorders

Acute kidney injury ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Respiratory, thoracic and mediastinal disorders

Chronic respiratory failure ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Dyspnoea ^{∗ A}

0 / 59 (0%)

3 / 39 (7.69%)

3 / 98 (3.06%)

Haemoptysis ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Haemothorax ^{∗ A}

2 / 59 (3.39%)

0 / 39 (0%)

2 / 98 (2.04%)

Pleural effusion ^{∗ A}

1 / 59 (1.69%)

1 / 39 (2.56%)

2 / 98 (2.04%)

Pneumothorax ^{∗ A}

0 / 59 (0%)

1 / 39 (2.56%)

1 / 98 (1.02%)

Vascular disorders

Hypertension ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

Peripheral embolism ^{∗ A}

1 / 59 (1.69%)

0 / 39 (0%)

1 / 98 (1.02%)

∗Indicates events were collected by non-systematic methods.
ATerm from vocabulary, MedDRA version 25.0

Other (Not Including Serious) Adverse Events

Frequency Threshold for Reporting Other Adverse Events

Treatment-Naive

Previously Treated

Total

Affected / At Risk (%)

Total

59 / 59 (100%)

38 / 39 (97.44%)

97 / 98 (98.98%)

Blood and lymphatic system disorders

Anaemia ^{∗ A}

20 / 59 (33.9%)

10 / 39 (25.64%)

30 / 98 (30.61%)

Eye disorders

Vision blurred ^{∗ A}

14 / 59 (23.73%)

6 / 39 (15.38%)

20 / 98 (20.41%)

Gastrointestinal disorders

Abdominal pain ^{∗ A}

14 / 59 (23.73%)

6 / 39 (15.38%)

20 / 98 (20.41%)

Abdominal pain upper ^{∗ A}

4 / 59 (6.78%)

4 / 39 (10.26%)

8 / 98 (8.16%)

Constipation ^{∗ A}

18 / 59 (30.51%)

8 / 39 (20.51%)

26 / 98 (26.53%)

Diarrhoea ^{∗ A}

29 / 59 (49.15%)

20 / 39 (51.28%)

49 / 98 (50%)

Nausea ^{∗ A}

37 / 59 (62.71%)

19 / 39 (48.72%)

56 / 98 (57.14%)

Vomiting ^{∗ A}

23 / 59 (38.98%)

13 / 39 (33.33%)

36 / 98 (36.73%)

General disorders

Asthenia ^{∗ A}

7 / 59 (11.86%)

9 / 39 (23.08%)

16 / 98 (16.33%)

Chills ^{∗ A}

3 / 59 (5.08%)

3 / 39 (7.69%)

6 / 98 (6.12%)

Fatigue ^{∗ A}

29 / 59 (49.15%)

16 / 39 (41.03%)

45 / 98 (45.92%)

Malaise ^{∗ A}

5 / 59 (8.47%)

1 / 39 (2.56%)

6 / 98 (6.12%)

Non-cardiac chest pain ^{∗ A}

6 / 59 (10.17%)

2 / 39 (5.13%)

8 / 98 (8.16%)

Oedema peripheral ^{∗ A}

12 / 59 (20.34%)

8 / 39 (20.51%)

20 / 98 (20.41%)

Pyrexia ^{∗ A}

16 / 59 (27.12%)

6 / 39 (15.38%)

22 / 98 (22.45%)

Infections and infestations

COVID-19 ^{∗ A}

5 / 59 (8.47%)

2 / 39 (5.13%)

7 / 98 (7.14%)

Investigations

Alanine aminotransferase increased ^{∗ A}

10 / 59 (16.95%)

3 / 39 (7.69%)

13 / 98 (13.27%)

Amylase increased ^{∗ A}

4 / 59 (6.78%)

2 / 39 (5.13%)

6 / 98 (6.12%)

Aspartate aminotransferase increased ^{∗ A}

11 / 59 (18.64%)

4 / 39 (10.26%)

15 / 98 (15.31%)

Blood alkaline phosphatase increased ^{∗ A}

9 / 59 (15.25%)

2 / 39 (5.13%)

11 / 98 (11.22%)

Blood creatine phosphokinase increased ^{∗ A}

10 / 59 (16.95%)

5 / 39 (12.82%)

15 / 98 (15.31%)

Blood creatinine increased ^{∗ A}

8 / 59 (13.56%)

7 / 39 (17.95%)

15 / 98 (15.31%)

Ejection fraction decreased ^{∗ A}

4 / 59 (6.78%)

4 / 39 (10.26%)

8 / 98 (8.16%)

Lipase increased ^{∗ A}

11 / 59 (18.64%)

4 / 39 (10.26%)

15 / 98 (15.31%)

Platelet count decreased ^{∗ A}

2 / 59 (3.39%)

4 / 39 (10.26%)

6 / 98 (6.12%)

SARS-CoV-2 test positive ^{∗ A}

4 / 59 (6.78%)

4 / 39 (10.26%)

8 / 98 (8.16%)

Weight decreased ^{∗ A}

6 / 59 (10.17%)

1 / 39 (2.56%)

7 / 98 (7.14%)

Weight increased ^{∗ A}

10 / 59 (16.95%)

1 / 39 (2.56%)

11 / 98 (11.22%)

Metabolism and nutrition disorders

Decreased appetite ^{∗ A}

12 / 59 (20.34%)

2 / 39 (5.13%)

14 / 98 (14.29%)

Dehydration ^{∗ A}

2 / 59 (3.39%)

3 / 39 (7.69%)

5 / 98 (5.1%)

Hyperglycaemia ^{∗ A}

4 / 59 (6.78%)

3 / 39 (7.69%)

7 / 98 (7.14%)

Hyperkalaemia ^{∗ A}

6 / 59 (10.17%)

1 / 39 (2.56%)

7 / 98 (7.14%)

Hypoalbuminaemia ^{∗ A}

4 / 59 (6.78%)

3 / 39 (7.69%)

7 / 98 (7.14%)

Hyponatraemia ^{∗ A}

7 / 59 (11.86%)

5 / 39 (12.82%)

12 / 98 (12.24%)

Musculoskeletal and connective tissue disorders

Arthralgia ^{∗ A}

9 / 59 (15.25%)

6 / 39 (15.38%)

15 / 98 (15.31%)

Back pain ^{∗ A}

11 / 59 (18.64%)

8 / 39 (20.51%)

19 / 98 (19.39%)

Muscle spasms ^{∗ A}

10 / 59 (16.95%)

2 / 39 (5.13%)

12 / 98 (12.24%)

Muscular weakness ^{∗ A}

5 / 59 (8.47%)

2 / 39 (5.13%)

7 / 98 (7.14%)

Myalgia ^{∗ A}

6 / 59 (10.17%)

4 / 39 (10.26%)

10 / 98 (10.2%)

Pain in extremity ^{∗ A}

6 / 59 (10.17%)

7 / 39 (17.95%)

13 / 98 (13.27%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Seborrhoeic keratosis ^{∗ A}

5 / 59 (8.47%)

2 / 39 (5.13%)

7 / 98 (7.14%)

Nervous system disorders

Dizziness ^{∗ A}

10 / 59 (16.95%)

6 / 39 (15.38%)

16 / 98 (16.33%)

Dysgeusia ^{∗ A}

5 / 59 (8.47%)

3 / 39 (7.69%)

8 / 98 (8.16%)

Headache ^{∗ A}

6 / 59 (10.17%)

4 / 39 (10.26%)

10 / 98 (10.2%)

Paraesthesia ^{∗ A}

5 / 59 (8.47%)

0 / 39 (0%)

5 / 98 (5.1%)

Psychiatric disorders

Insomnia ^{∗ A}

7 / 59 (11.86%)

3 / 39 (7.69%)

10 / 98 (10.2%)

Renal and urinary disorders

Pollakiuria ^{∗ A}

6 / 59 (10.17%)

0 / 39 (0%)

6 / 98 (6.12%)

Respiratory, thoracic and mediastinal disorders

Cough ^{∗ A}

11 / 59 (18.64%)

6 / 39 (15.38%)

17 / 98 (17.35%)

Dyspnoea ^{∗ A}

16 / 59 (27.12%)

7 / 39 (17.95%)

23 / 98 (23.47%)

Productive cough ^{∗ A}

8 / 59 (13.56%)

3 / 39 (7.69%)

11 / 98 (11.22%)

Skin and subcutaneous tissue disorders

Alopecia ^{∗ A}

9 / 59 (15.25%)

3 / 39 (7.69%)

12 / 98 (12.24%)

Dry skin ^{∗ A}

11 / 59 (18.64%)

2 / 39 (5.13%)

13 / 98 (13.27%)

Hair texture abnormal ^{∗ A}

5 / 59 (8.47%)

1 / 39 (2.56%)

6 / 98 (6.12%)

Hyperkeratosis ^{∗ A}

4 / 59 (6.78%)

1 / 39 (2.56%)

5 / 98 (5.1%)

Pruritus ^{∗ A}

7 / 59 (11.86%)

8 / 39 (20.51%)

15 / 98 (15.31%)

Rash ^{∗ A}

6 / 59 (10.17%)

5 / 39 (12.82%)

11 / 98 (11.22%)

Rash maculo-papular ^{∗ A}

5 / 59 (8.47%)

3 / 39 (7.69%)

8 / 98 (8.16%)

Vascular disorders

Hypertension ^{∗ A}

8 / 59 (13.56%)

2 / 39 (5.13%)

10 / 98 (10.2%)

∗Indicates events were collected by non-systematic methods.
ATerm from vocabulary, MedDRA version 25.0

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact:

Name/Official Title:

Pfizer ClinicalTrials.gov Call Center

Organization:

Pfizer Inc.

Phone:

1-800-718-1021

Email:

ClinicalTrials.gov_Inquiries@pfizer.com