Clinical trial

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

Name

W00090 GE 2 01

Description

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.

Trial arms

Trial start

2019-01-17

Estimated PCD

2020-06-29

Trial end

2023-04-27

Status

Completed

Phase

Early phase I

Treatment

encorafenib

300 mg administered orally once daily (QD)

Arms:

1 Arm

Other names:

Braftovi

Binimetinib

Binimetinib 45 mg administered orally twice daily (BID)

Arms:

1 Arm

Other names:

Mektovi

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.

Arms:

1 Arm

Other names:

Erbitux

Size

Primary endpoint

Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments

From initiation of treatment to disease progression up to a maximum of 17.6 months.

Eligibility criteria

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'All involved know the identity of the intervention assignment.'}}, 'enrollmentInfo': {'count': 95, 'type': 'ACTUAL'}}

Updated at

2024-02-02

1 organization

Organization

Pierre Fabre Medicament