Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 15 May 2023
• Main ID: NCT02928224
• Date of registration: 16/08/2016
• Prospective Registration: Yes
• Primary sponsor: Pfizer
• Public title: Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer BEACON CRC
• Scientific title: A Multicenter, Randomized, Open-label, 3-Arm Phase 3 Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer
• Date of first enrolment: October 13, 2016
• Target sample size: 702
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02928224
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Pfizer CT.gov Call Center
• Affiliation: Pfizer

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- Age = 18 years at time of informed consent

- Histologically- or cytologically-confirmed CRC that is metastatic

- Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any
time prior to Screening or by the central laboratory

- Progression of disease after 1 or 2 prior regimens in the metastatic setting

- Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1

- Adequate bone marrow, cardiac, kidney and liver function

- Able to take oral medications

- Female patients are either postmenopausal for at least 1 year, are surgically sterile
for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy
from screening through follow-up if of childbearing potential

- Males must agree to take appropriate precautions to avoid fathering a child from
screening through follow-up

Key Exclusion Criteria:

- Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other
epidermal growth factor receptor (EGFR) inhibitors

- Prior irinotecan hypersensitivity or toxicity that would suggest an inability to
tolerate irinotecan 180 mg/m2 every 2 weeks

- Symptomatic brain metastasis or leptomeningeal disease

- History or current evidence of retinal vein occlusion or current risk factors for
retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of
hyperviscosity or hypercoagulability syndromes)

- Known history of acute or chronic pancreatitis

- History of chronic inflammatory bowel disease or Crohn's disease requiring medical
intervention (immunomodulatory or immunosuppressive medications or surgery) =12 months
prior to randomization

- Uncontrolled blood pressure despite medical treatment

- Impaired GI function or disease that may significantly alter the absorption of
encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting,
malabsorption syndrome, small bowel resection with decreased intestinal absorption)

- Concurrent or previous other malignancy within 5 years of study entry, except cured
basal or squamous cell skin cancer, superficial bladder cancer, prostate
intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or
indolent malignancy

- History of thromboembolic or cerebrovascular events = 6 months prior to starting study
treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein
thrombosis or pulmonary emboli

- Concurrent neuromuscular disorder that is associated with the potential of elevated
creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy,
amyotrophic lateral sclerosis, spinal muscular atrophy)

- Residual common terminology criteria for adverse events (CTCAE) = Grade 2 toxicity
from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2
neuropathy

- Known history of HIV infection

- Active hepatitis B or hepatitis C infection

- Known history of Gilbert's syndrome

- Known contraindication to receive cetuximab or irinotecan at the planned doses



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

BRAF V600E-mutant Metastatic Colorectal Cancer

Intervention(s)

Drug: Encorafenib

Drug: 5-Fluorouracil

Drug: Irinotecan

Drug: Cetuximab

Drug: Folinic Acid

Drug: Binimetinib

Primary Outcome(s)

(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Number of Participants With Dose-limiting Toxicities (DLTs) [Time Frame: Cycle 1 (up to 28 days)]

(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Number of Participants With Adverse Events (AEs) [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

Secondary Outcome(s)

(Phase 3) Change From Baseline in the EuroQol-5D-5L (EQ-5D-5L) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib [Time Frame: 2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.]

(Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib [Time Frame: 2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.]

(Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab [Time Frame: 2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.]

(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Cetuximab [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Phase 3) Change From Baseline in the Patient Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Encorafenib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Metabolite of Binimetinib (AR00426032) [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032) [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Duration of Response (DOR) by Investigator [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Response Rate (ORR) by Investigator [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Binimetinib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032) [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Progression-free Survival (PFS) by BICR [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Response Rate (ORR) by BICR [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Time to Response by Investigator [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

(Safety Lead-in) Progression-free Survival (PFS) by Investigator [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Time to Response by BICR [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Duration of Response (DOR) by BICR [Time Frame: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)]

(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib [Time Frame: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2]

Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR [Time Frame: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)]

Secondary ID(s)

BEACON CRC

2015-005805-35

ARRAY-818-302

C4221009

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ono Pharmaceutical Co. Ltd

Merck KGaA, Darmstadt, Germany

Pierre Fabre Medicament

Results

• Results available: Yes
• Date Posted: 14/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02928224