Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer (ANCHOR-CRC)

Phase II, Open-label, Single Arm, Multicenter Study of Encorafenib, Binimetinib Plus Cetuximab in Subjects With Previously Untreated BRAF V600E -Mutant Metastatic Colorectal Cancer

The purpose of this study is to evaluate the efficacy and safety of the combination of study drugs encorafenib, binimetinib and cetuximab in patients who have BRAF V600 mutant metastatic colorectal cancer and have not received any prior treatment for their metastatic disease.

Study Overview

• Status: Completed
• Conditions: BRAF V600E-mutant Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: encorafenib; Drug: Binimetinib; Drug: Cetuximab

Detailed Description

The presence of a BRAFV600E mutation is considered a marker of poor prognosis in subjects with mCRC. The preclinical results and preliminary clinical data together justify the evaluation of this triple combination in the first-line setting of this population. The primary objective of the study is to evaluate the antitumor activity of the combination of encorafenib, binimetinib and cetuximab by assessing the overall response rate in adult subjects with previously untreated BRAFV600E-mutant metastatic colorectal cancer. It will also assess the effect of the triple combination on the duration of response, time to response, progression-free survival and overall survival and assess the effect on quality of life. It will also characterize the safety and tolerability of the triple combination as well as describe the pharmacokinetics (PK) of encorafenib, binimetinib, and cetuximab.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1020
    • Krankenhaus der Barmherzigen Brüder
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • East Flanders
    • Gent, East Flanders, Belgium, 9000
      • UZ Gent, Gastro-Enterology
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Trial DIO, UZ Gasthuisberg
• France
  • Brest, France, 29200
    • Hôpital Morvan CHRU de Brest Institut de cancérologie et d'hematologie
  • Marseille, France, 13005
    • AP-HM CHU Timone
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Paris, France, 75014
    • Hôpital Cochin Gastroenterology
  • Pessac, France, 33604
    • HOPITAL HAUT-LEVEQUE, Av de MAGELLAN
  • Saint-Herblain, France, 44805
    • ICO- Site René Gauducheau
  • Toulouse, France
    • CHU Toulouse Rangueil
  • Cedex 5
    • Montpellier, Cedex 5, France, 34298
      • ICM- VAL d 'Aurelle
• Italy
  • Candiolo, Italy, 10060
    • Fondazione Del Piemonte Per L'Oncologia Ircc Candiolo
  • Genova, Italy, 16132
    • Ospedale Policlinic San Martin
  • Perugia, Italy, 06129
    • Ospedale S.M. Misericordia
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo della Sofferenza
  • Forlì-Cesena
    • Meldola, Forlì-Cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Pierre Fabre Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Pierre Fabre Investigative Site
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • Pierre Fabre Investigative Site
  • Osaka
    • Osaka-shi, Osaka, Japan, 540-0006
      • Pierre Fabre Investigative Site
  • Shizuoka
    • Nagaizumi-cho, Shizuoka, Japan, 411-8777
      • Pierre Fabre Investigative Site
  • Tokyo
    • Koto-ku,, Tokyo, Japan, 135-8550
      • Pierre Fabre Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3543 AZ
    • St Antonius Ziekenhuis
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08908
    • Institut Català d'Oncologia (ICO L'Hospitalet)
  • Barcelona, Spain
    • Hospital de la Santa Creu i Santa Pau
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de
  • Vigo, Spain, 36312
    • Hospital Álvaro Cunqueiro
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Community Of Madrid
    • Madrid, Community Of Madrid, Spain, 28220
      • Hospital Puerta de Hierro
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Complejo Hospitalario De Navarra S Oncologia Medica
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom, LS9 7TF
    • St James Hospital
  • London, United Kingdom, SE1 9RT
    • GI research team, OHCT, Guy's Hospital
  • Manchester, United Kingdom, M20 4BX
    • GI Research Team, The Christie NHS Foundation Trust
  • Devon
    • Torquay, Devon, United Kingdom, TQ2 7AA
      • Torbay Hospital, Lowes Bridge
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • The Royal Marsden NHS Foundation Trust
• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • PC dba West Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥ 18 years of age
• Histologically or cytologically confirmed CRC that is metastatic
• Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening
• Evidence of measurable disease as per RECIST, v1.1
• Subject able to receive cetuximab as per approved label with regards to RAS status
• Eastern Cooperative Oncology Group Status (ECOG) 0 or 1
• Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes as per protocol
• Subject able to take oral medications

Exclusion Criteria:

• Prior systemic therapy for metastatic disease
• Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab or other anti-EGFR inhibitors
• Symptomatic brain metastasis or Leptomeningeal disease
• History or current evidence of Retinal Vein Occlusion (RVO) or current risk factors for RVO
• History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to first dose.
• Impaired cardiovascular function or clinically significant cardiovascular diseases: history of myocardial infarction or coronary disorders within 6 months prior to start of study treatment, symptomatic congestive heart failure (grade 2 or higher), past or current clinically significant arrhythmia and/or conduction disorder within 6 months prior to study treatment start
• History of thromboembolic or cerebrovascular events within 6 months prior to start of study treatment
• Concurrent neuromuscular disorder that is associated with potential elevation of Creatine Kinase
• Known contraindication to cetuximab administration as per SPC/approved label

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1 Arm; encorafenib plus binimetinib plus cetuximab

Drug: encorafenib; 300 mg administered orally once daily (QD); Other Names: Braftovi; Drug: Binimetinib; Binimetinib 45 mg administered orally twice daily (BID); Other Names: Mektovi; Drug: Cetuximab; Standard of care for the 28 first weeks(*) and then every 2 weeks (**) : (*) 400 mg/m2 administered as a 120-min infusion on Cycle 1 Day 1, followed by 250 mg/m2 administered as a 60-min infusion once weekly (QW) for the first 28 weeks. (**) 500 mg/m2 administered as a 120-min infusion twice weekly (Q2W) from Week 29 (Cycle 8 Day 1) onward. Following implementation of an Urgent Safety Measure on 26 Mar 2020 due to the outbreak of COVID-19 pandemic, cetuximab infusions could be administered Q2W regardless of the cycle number, after investigator's evaluation of the benefit/risk ratio for the subject, with regards to COVID-19 pandemic.; Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments	The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.	From initiation of treatment to disease progression up to a maximum of 17.6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment	The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.	From initiation of treatment to disease progression up to a maximum of 17.6 months
Overall Response Rate (ORR) Based on Local Tumor Assessments	The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.	From initiation of treatment to disease progression up to a maximum of 17.6 months
Overall Response Rate (ORR) Based on Central Tumor Assessments	The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.	From initiation of treatment to disease progression up to a maximum of 17.6 months
Duration of Response (DOR) Per Local Assessment	Time from first radiographic evidence of response based on local radiologist/investigator review to the earliest documented PD or death due to underlying disease	From first radiographic evidence of response to disease progression up to a maximum of 17.6 months
Duration of Response (DOR) Per Central Assessment	Time from first radiographic evidence of response based on central review to the earliest documented PD or death due to underlying disease	From first radiographic evidence of response to disease progression up to a maximum of 17.6 months
Time to Response (TTR) Per Local Review	The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per local review	From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months
Time to Response (TTR) Per Central Review	The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per central review	From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months
Progression-Free Survival (PFS) Per Local Review	Time from first dose to the earliest documented date of disease progression based on local radiologist/investigator review or death due to any cause	From initiation of treatment to disease progression or death up to a maximum of 17.6 months
Progression of Free Survival (PFS) Per Central Review	Time from first dose to the earliest documented date of disease progression based on central review or death due to any cause	From initiation of treatment to disease progression or death up to a maximum of 17.6 months
Overall Survival (OS)	Time from first dose to death due to any cause	From initiation of treatment to death up to a maximum of 17.6 months
Plasma Concentration of Encorafenib	Plasma concentration of encorafenib	2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)
Plasma Concentration of Binimetinib	Plasma concentration of binimetinib	2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)
Plasma Concentration of Cetuximab	Plasma concentration of cetuximab	2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)
Change From Baseline in EORTC QLQ-C30 Over Time	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for cancer subjects (EORTC QLQ-C30) includes a global health status/QoL. The scale ranges in score from 0 to 100, higher score on the global health status/QoL scale indicate higher QoL. Changes from baseline in EORTC QLQ-C30 global health status/quality of life (QoL) over time are presented in this record.	From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months
Change From Baseline in EQ-5D-5L Over Time	The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L VAS records the patient's self-rated health on a vertical visual analogue scale numbered from 0 ("The worst health you can imagine") to 100 ("The best health you can imagine"). Changes from baseline in EQ-5D-5L VAS over time are presented in this record.	From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months
PGIC Scores Over Time	The Patient Global Impression of Change (PGIC) is a measure of patients' perceptions of change in their symptoms over time. For this assessment, subjects answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse."	From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months

Collaborators and Investigators

• Sponsor: Pierre Fabre Medicament
• Collaborators: Pfizer; Merck KGaA, Darmstadt, Germany; Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Isabelle KLAUCK, MD, Corporate Medical&Patient/Consumer Division, Pierre Fabre Medicament

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): June 29, 2020
• Study Completion (Actual): April 27, 2023

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (Actual): October 2, 2018

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: W00090 GE 2 01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No