A Study to Characterize Encorafenib Plus Cetuximab as Rechallenge Treatment for BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy With BRAF Inhibitors-based Combinations

NCT07178717 | Not Yet Recruiting Phase 2

• 2 other identifiers: VHIO230042023-509564-22-00
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, unicentre, single-arm Phase 2 study of encorafenib and cetuximab as rechallenge treatment in patients with BRAF V600E-mutant metastatic colorectal cancer after previous therapy with BRAF inhibitors-based combinations. The study aims to evaluate the antitumor activity of encorafenib plus cetuximab as a rechallenge strategy measured by progression-free survival rate at 4 months. Eligible patients (a total of 25) will receive encorafenib 300 mg (four 75 mg capsules) once daily (q.d) in 28-day cycles plus intravenous cetuximab at 500 mg/m2 every 2 weeks (Q2W). Treatment will be administered until progression, unacceptable toxicity, patient request, physician's decision or subsequent anticancer therapy.

Conditions

Colo-rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression-free survival rate at 4 months (4-month PFS rate) according to RECIST V1.1 by Investigator assessment.

  4 months since the start of treatment

Secondary Outcomes (5)

• Progression-free survival

  From randomization until the first documented progression, assessed up to 30 months (expected)

• Objective response rate

  For the duration of the study, expected 30 months

• Overal Survival

  From date of enrollment until death, up to the duration of the study (expected 30 months)

• Evaluate the safety and tolerability profile

  Through study completion, an average of 1 year

• Clinical efficacy

  Through study completion, an average of 1 year"

Study Arms (1)

Bevacizumab + encorafenib

EXPERIMENTAL

Drug: Rechalange with bevacizumab + encorafenib

Interventions

Rechalange with bevacizumab + encorafenib DRUG

Patients will receive encorafenib 300mg once daily plus cetuximab 500mg/m2 every 2 weeks until disease progression, unacceptable toxicity, patient request, physician's decision to withdraw treatment, subsequent anticancer therapy or death.

Bevacizumab + encorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form.
• Age ≥18 years at the time of informed consent.
• Histologically- or cytologically confirmed mCRC that is metastatic.
• Presence of confirmed BRAF V600E mutation.
• Eligible to receive cetuximab and encorafenib per locally approved label with regard to tumor RAS status.
• Patients must be previously treated with at least 2 prior regimens for metastatic disease and had demonstrated progressive disease or intolerance to their last regimen. Prior standard chemotherapy must include the following agents: fluoropyrimidine in monotherapy or in combination with irinotecan and/or oxaliplatin with or without anti-VEGF. Combination of chemotherapy with BRAF inhibitor-containing regimen is also permitted.
• Patients must have received BRAF inhibitor plus anti-EGFR combinations (including but not limited to MEK or ERK inhibitors or chemotherapy) treatment for ≥ 4 months. Patients must have had complete response, partial response or stable disease \>6 months during the BRAF inhibitor-based treatment.
• Patients at study enrollment should have at least 4 months interval since the last administration of BRAF inhibitors.
• Life expectancy \>12 weeks, as determined by the investigator.
• Patients must have progressed during or within 6 months of the last chemotherapy regimen \> Patients who received adjuvant/neoadjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant/neoadjuvant chemotherapy are permitted to count the adjuvant/neoadjuvant therapy as one regimen for advanced disease.
• Measurable disease according to RECIST v1.1.
• ECOG performance status 0-1.
• Adequate bone marrow function characterized by the following at screening:
• Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L.
• Platelets ≥100 x 10\^9/L.

You may not qualify if:

• Treatment with another investigational drug or participation in another investigational study at enrolment or within 30 days prior to enrollment.
• Patient is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
• Known history of chronic pancreatitis.
• Tumors with microsatellite instability or mismatch repair deficiency if they have not received a PD1/PDL1 inhibitor-based treatment, unless medical contraindication.
• History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months before the enrollment in the study.
• Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
• History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft \[CABG\], coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment.
• Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality ≤ 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia.
• Impaired hepatic function, defined as Child-Pugh class B or C.
• Known history of human immunodeficiency virus (HIV), active hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients with past exposure to HBV are also eligible for the study provided they are negative for HBV DNA.
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study.
• Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and the enrollment in the study.
• Subjects with leptomeningeal carcinomatosis.
• Impaired gastrointestinal (GI) function or disease that may significantly alter the absorption of encorafenib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).
• Knowledge of any other disease or medication that may interfere with study treatment.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead

Study Sites (1)

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Bevacizumab; encorafenib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 17, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)