Clinical trial NCT03915951: An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
Official title: A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: lung cancer
cancer
non-small cell lung cancer
non small cell lung cancer
NSCLC
Encorafenib
Binimetinib
Phase 2
Open Label
BRAF mutation
BRAF V600E
Array
Stage IV NSCLC
Metastatic NSCLC
PDL1
PD-LI
Immunotherapy
First line platinum based chemotherapy
BRAF inhibitor
V600
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter, non-randomized, Phase 2 study to determine the safety, tolerability and efficacy of encorafenib given in combination with binimetinib in patients with BRAFV600E-mutant metastatic non-small cell lung cancer (NSCLC). Patients who are either treatment-naïve, OR who have received 1) first-line treatment with standard platinum-based chemotherapy, OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy will be enrolled.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)
timeFrame: From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)
Secondary outcomes:
measure: Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment
timeFrame: From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months)
measure: Duration of Response (DoR) by IRR and Investigator Assessments
timeFrame: 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)
measure: Disease Control Rate (DCR) by IRR and Investigator Assessments
timeFrame: After 24 Weeks (≥168 days) from the date of first dose of study intervention
measure: Progression-free Survival (PFS) by IRR and Investigator Assessments
timeFrame: 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)
measure: Time to Response (TTR) by IRR and Investigator Assessments
timeFrame: From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months)
measure: Kaplan-Meier Estimates of Overall Survival (OS)
timeFrame: The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Number of Participants With Notable Abnormal Vital Signs
timeFrame: 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)
measure: Number of Participants With Notable ECG (QTcF) Values
timeFrame: Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)
measure: Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade
timeFrame: Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)
Other outcomes:
Locations:
city: Yuma
country: United States
facility: Yuma Regional Medical Center Cancer Center
state: Arizona
city: Yuma
country: United States
facility: Yuma Regional Medical Center Ophthalmology
state: Arizona
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Santa Monica
country: United States
facility: UCLA Stein Eye Center Santa Monica (OPH)
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Altamonte Springs
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Bonita Springs
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Brandon
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Cape Coral
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Clearwater
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Fleming Island
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Largo
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Lecanto
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Naples
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Ocala
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Orange City
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Orlando
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Port Charlotte
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Spring Hill
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists PAN - SCRI - PPDS
state: Florida
city: Tampa
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Tavares
country: United States
facility: Florida Cancer Specialist
state: Florida
city: The Villages
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Trinity
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Venice
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Venice
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Winter Park
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute @ Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute @ Emory Saint Joseph's Hospital
state: Georgia
city: Johns Creek
country: United States
facility: Winship Cancer Institute @ Emory Johns Creek Hospital
state: Georgia
city: Overland Park
country: United States
facility: MidAmerica Division, Inc. c/o Menorah Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins Wilmer Eye Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston (OCB)
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston Inc
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center - 330 Brookline Ave
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center/East
state: Massachusetts
city: Newton
country: United States
facility: Dana-Farber Cancer Institute - Chestnut Hill
state: Massachusetts
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Independence
country: United States
facility: MidAmerica Division, Inc. c/o Centerpoint Medical Center
state: Missouri
city: Kansas City
country: United States
facility: MidAmerica Division, Inc., c/o Research Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center Basking Ridge
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Paramus
country: United States
facility: Metropolitan Eye Care
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
state: New York
city: New York
country: United States
facility: Weill Cornell Eye Associates
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State CarePoint East
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University East Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University James Cancer Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center - Thoracic Oncology Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State Eye and Ear Institute
state: Ohio
city: Columbus
country: United States
facility: Stefanie Spielman Comprehensive Breast Cancer
state: Ohio
city: Columbus
country: United States
facility: Martha Morehouse Medical Plaza
state: Ohio
city: Gahanna
country: United States
facility: Ohio State CarePoint Gahanna
state: Ohio
city: Lewis Center
country: United States
facility: Ohio State Outpatient Care Lewis Center
state: Ohio
city: Westerville
country: United States
facility: The Ohio State University East Hospital Ohio State Outpatient Care New Albany
state: Ohio
city: Clackamas
country: United States
facility: Providence Cancer Institute Clackamas Clinic
state: Oregon
city: Newberg
country: United States
facility: Providence Cancer Institute Newberg Clinic
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Institute, Franz Clinic
state: Oregon
city: Portland
country: United States
facility: Providence Oncology and Hematology Care Clinic - Westside
state: Oregon
city: Erie
country: United States
facility: UPMC Hillman Cancer Center Erie
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Hillman Cancer Center - Arnold Palmer - Mt View
state: Pennsylvania
city: Monroeville
country: United States
facility: UPMC Hillman Cancer Center Monroeville
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Eye Center, Eye and Ear Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center - Passavant (HOA)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center - Passavant (OHA)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center - Upper St. Clair
state: Pennsylvania
city: York
country: United States
facility: Weaver Eye Associates
state: Pennsylvania
city: York
country: United States
facility: WellSpan Oncology Research
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Cleveland
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dickson
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Hendersonville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Hermitage
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Murfreesboro
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Shelbyville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Houston
country: United States
facility: Houston Eye Associates - Gramercy Location
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Millennium Research & Clinical Development
state: Texas
city: Seattle
country: United States
facility: Eye associates Northwest
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Milan
country: Italy
facility: Departimento Oncologia Medica
state: Lombardia
city: Milan
country: Italy
facility: Unita Operativa di Oculistica: UO Oncologia Oculare e Immunopatologia oculare
state: Lombardia
city: Milan
country: Italy
facility: Unita Operativa Radiologia
state: Lombardia
city: Milan
country: Italy
facility: UO Anatomia e lstologia Patologica
state: Lombardia
city: Milan
country: Italy
facility: UO Dermatologia e Cosmetologia
state: Lombardia
city: Milan
country: Italy
facility: UO Medicina Nucleare
state: Lombardia
city: Orbassano
country: Italy
facility: S.S.D. Oncologia Polmonare
state: Torino
city: Orbassano
country: Italy
facility: SCDO Cardiologia
state: Torino
city: Orbassano
country: Italy
facility: SCDU Anatomia Patologica
state: Torino
city: Orbassano
country: Italy
facility: SCDU Oftalmologia
state: Torino
city: Orbassano
country: Italy
facility: SCDU Radiodiagnostica e S.S. Medicina Nucleare
state: Torino
city: Torino
country: Italy
facility: Dermatologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
state: TO
city: Bologna
country: Italy
facility: UO Dermatologia Centro Tumori Cutanei (CTC)- Azienda Ospedaliero
city: Bologna
country: Italy
facility: UO di Oftalmologia- Azienda Ospedaliero Universitaria Di Bologna
city: Bologna
country: Italy
facility: UO Medicina Borghi- Azienda Ospedaliero Universitaria Di Bologna
city: Bologna
country: Italy
facility: UO Radiologia Golfieri- Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
city: Bologna
country: Italy
facility: UOC di Anatomia Patologica- Azienda Ospedaliero Universitaria Di Bo logna
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Napli
country: Italy
facility: Clinica Oculistica II, 2° Policlinico Federico II
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
city: Napoli
country: Italy
facility: S. C. Farmacia
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
state: Noord-holland
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
city: Amsterdam
country: Netherlands
facility: OLVG, locatie Oost; Ophthalmology department
city: Groningen
country: Netherlands
facility: Ophthalmology department
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General
state: Málaga
city: Badalona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: CETIR Centro Medico Teknon
city: Barcelona
country: Spain
facility: Hospital Quiron Salud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Universitario Vall d'Hebron
city: Cordoba
country: Spain
facility: Grupo Cardiologico Corpal (Hospital de la Cruz Roja)
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Esplugues de Llobregat
country: Spain
facility: Cetir
city: L'Hospitalet
country: Spain
facility: lnstitut Catala d'Oncologia_L'Hospitalet
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Centro Hospitalario Integral Privado (CHIP)
city: Sevilla
country: Spain
facility: CERCO
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.