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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer

Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer

Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer (NCT06207656) is a Phase 2 interventional studying Colorectal Cancer, sponsored by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

As a result of the little benefit obtained from standard treatments and the poor prognosis of these patients, the BRAF-V600E mutant MSS aCRC represents an unmet medical need requiring clinical research. The combination of encorafenib, cetuximab and binimetinib as second- or third-line treatment for mCRC resulted in significantly better outcomes than standard therapy in a phase 3 clinical trial, which also revealed treatment safety and tolerability to be acceptable. Compared to the control group (cetuximab and irinotecan or cetuximab and FOLFIRI), the triplet therapy cohort showed higher median overall survival (9.3 vs. 5.9 months) and response rates (26.8% vs. 1.8%). Grade 3 adverse events occurred in 65.8% and 64.2% of patients for triple-therapy and control groups, respectively. Based on these results, the investigators speculated that the combination of encorafenib, cetuximab and binimetinib could be used as induction therapy to improve treatment outcomes in BRAF-V600E-mutated MSS aCRC locally advanced initially unresectable but potentially resectable; initially resectable or initially unresectable but potentially resectable oligometastatic disease; and in patients with stage II-IV who have relapsed after chemotherapy (neo and/or adjuvant) or surgery, if the shorter time after resection or from treatment end to relapse is longer than 6 months.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Colorectal Cancer and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 70 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Colorectal Cancer subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 1\. Male or female participants age ≥18 years at the time of willing to sign a consent form. 2. Capable of giving signed willing to sign a consent form/assent. 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 4\. Participants with diagnosed by tissue sample (biopsy-confirmed) colorectal adenocarcinoma. 5\. Presence of a BRAF V600E mutation confirmed as per standard of care according to international guidelines at any time prior to Screening. 6\. Microsatellite stable (MSS) or Mismatch-Repair proficient (pMMR) disease confirmation assessed by local PCR or immunohistochemistry (IHC). 7\. Participants with CRC who have one of these criteria: 1. Locally advanced colorectal cancer with initially unresectable but potentially resectable disease according to the local Multidisciplinary Tumour Board (MTB). 2. Oligometastatic colorectal cancer (possible metastasis sites: liver, lung, lymph nodes and peritoneum) with: i. Initially resectable disease according to the local MTB or ii. Initially unresectable but potentially resectable disease according to the local MTB c. Stage II-IV colorectal cancer treated with previous neoadjuvant and/or adjuvant chemotherapy, for R0, if the shorter time from the resection or from the end of the adjuvant treatment to the relapse of colorectal cancer (possible metastasis sites: liver, lung, lymph nodes and peritoneum) is longer than 6 months. This relapse (locoregional and/or systemic) should be initially resectable or initially unresectable but potentially resectable disease according to the local MTB 8. You should be able to carry out daily activities with 0 level of ability (ECOG 0) or 1. 9. Measurable or evaluable disease as assessed by investigator, according to RECIST v1.1. 10\. Adequate bone marrow function characterized by the following at screening: ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 1\. Male or female participants age ≥18 years at the time of informed consent. 2. Capable of giving signed informed consent/assent. 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 4\. Participants with histologically or cytologically confirmed colorectal adenocarcinoma. 5\. Presence of a BRAF V600E mutation confirmed as per standard of care according to international guidelines at any time prior to Screening. 6\. Microsatellite stable (MSS) or Mismatch-Repair proficient (pMMR) disease confirmation assessed by local PCR or immunohistochemistry (IHC). 7\. Participants with CRC who have one of these criteria: 1. Locally advanced colorectal cancer with initially unresectable but potentially resectable disease according to the local Multidisciplinary Tumour Board (MTB). 2. Oligometastatic colorectal cancer (possible metastasis sites: liver, lung, lymph nodes and peritoneum) with: i. Initially resectable disease according to the local MTB or ii. Initially unresectable but potentially resectable disease according to the local MTB c. Stage II-IV colorectal cancer treated with previous neoadjuvant and/or adjuvant chemotherapy, for R0, if the shorter time from the resection or from the end of the adjuvant treatment to the relapse of colorectal cancer (possible metastasis sites: liver, lung, lymph nodes and peritoneum) is longer than 6 months. This relapse (locoregional and/or systemic) should be initially resectable or initially unresectable but potentially resectable disease according to the local MTB 8. ECOG performance status of 0 or 1. 9. Measurable or evaluable disease as assessed by investigator, according to RECIST v1.1. 10\. Adequate bone marrow function characterized by the following at screening: 1. ANC ≥1.5 × 109/L 2. Platelets ≥100 × 109/L 3. Hemoglobin ≥9.0 g/dL (with or without blood transfusions). 11. Adequate hepatic and renal function characterized by the following at screening: <!-- --> 1. Serum total bilirubin ≤1.5 x ULN. Note 1: Total bilirubin \>1.5 x ULN is allowed if direct (conjugated) ≤1.5 x ULN and indirect (unconjugated) bilirubin is ≤4.25 x ULN. Note 2: Participants with hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled following discussion and agreement with the medical monitor. 2. ALT and AST ≤2.5 × ULN, or ≤5 × ULN in the presence of liver metastases. 3. Adequate renal function defined by an estimated creatinine clearance ≥50 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance, or according to local institutional standard method. 12\. Able to swallow, retain, and absorb oral medications. Exclusion Criteria: * 1\. Any medical or psychiatric condition including recent (within the past year) or current suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. 2\. Leptomeningeal disease or brain metastases. 3. History of chronic inflammatory bowel disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to the start of study treatment. 4\. Known RAS-mutant colorectal adenocarcinoma. 5. Impaired gastrointestinal function (e.g., uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, small bowel resection) or disease which may significantly alter the absorption of oral study intervention or recent changes in bowel function suggesting current or impending bowel obstruction. 6\. Clinically significant cardiovascular diseases, including any of the following: 1. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) ≤6 months prior to the start of study treatment. 2. Congestive heart failure requiring treatment (New York Heart Association Grade ≥2). 3. History or presence of clinically significant cardiac arrhythmias (including uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia). 4. History of thromboembolic or cerebrovascular events ≤12 weeks prior to the start of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e., massive or sub-massive) deep vein thrombosis or pulmonary emboli. Note 1: Participants with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they have been on a stable dose of anticoagulants for at least 4 weeks. Note 2: Participants with thromboembolic events related to indwelling catheters (including PICC lines) or other procedures may be enrolled. 5. Triplicate average QTcF interval ≥480 ms or a history of prolonged QT syndrome. 6. Congenital LQTS. 7. Evidence of active non-infectious pneumonitis. 8. Evidence of active and uncontrolled bacterial or viral infection, with certain exceptions, as noted below, for chronic infection with HIV, hepatitis B or hepatitis C (please see below), within 2 weeks prior to start of study treatment. 9\. Participants positive for HIV are ineligible unless they meet all of the following: <!-- --> 1. A stable regimen of highly active anti-retroviral therapy that is not contraindicated. 2. No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections. 3. A CD4 count \>250 cells/mcL, and an undetectable HIV viral load on standard PCR-based tests. 10\. Active hepatitis B or hepatitis C infection a. Active HBV is defined as any of the following: 1. HBsAg (+), HBV DNA \>200 IU/mL (105 copies/mL); 2. HBsAg (+), HBV DNA ≤200 IU/mL and persistent or intermittent elevation of ALT/AST and/or liver biopsy showing chronic hepatitis with moderate or severe necroinflammation. Note: Participants who are HBsAg (-), HBcAb (+) are eligible and should be monitored/treated as per local standard of care. b. Active HCV is defined as: 1. HCV antibody positive; AND 2. Presence of HCV RNA. 11. Concurrent or previous other malignancy within 3 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen's disease or prostate cancer with a Gleason score ≤6. Participants with other curatively treated malignancies with low risk of recurrence not listed may also be considered eligible after review and approval by the medical monitor. 12\. Residual CTCAE≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy. 13\. Previous treatment with any selective BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) and/or any selective MEK inhibitor prior to screening. 14\. Use of any prohibited medication (including herbal medication), supplement or food that is a moderate or strong inhibitor or inducer of CYP3A4/5 ≤1 week prior to the start of study intervention. 15\. Major surgery (e.g., inpatient procedure with regional or general anesthesia) or completion of radiation therapy ≤4 weeks prior to the start of study treatment. 16\. Previous systemic anticancer therapy for CRC, with the following exceptions: • Patients with resected (R0 or R1 resections) metastasis of CRC treated with or without adjuvant or neoadjuvant chemotherapy (+/- antiEGFR or bevacizumab) would be includible if the time from the resection or from the end of the adjuvant treatment (the later) to the relapse of CRC were longer than 6 months • Patients with previous adjuvant or neoadjuvant chemotherapy for resected St II/III CRC would be eligible if the time from the resection or from the end of the adjuvant treatment (the later) to the relapse of CRC were longer than 6 months 17. Prior systemic regimen in first line treatment for metastatic CRC in patients with unresectable or non-potentially resectable metastatic (M1) disease. 18\. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). 19\. Known contraindication to receiving cetuximab including hypersensitivity or toxicity that would suggest an inability to tolerate maximum cetuximab dose of 500 mg/m2. 20\. Known sensitivity or contraindication to any component of study intervention or their excipients at the planned doses. 21\. Pregnant, or is breastfeeding (lactating). 22. Male or female of childbearing age who do not agree with taking highly effective contraceptive precautions, (for definition, please refer to Appendix 15) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and men. 23\. Full dose radiotherapy \<28 days prior to the start of study treatment. Short course radiotherapy for local control of primary tumor or other palliative indication is allowed. 24\. Patients with ulcerative keratitis.

Treatments Being Tested

DRUG

EBC

Patients will receive the following per 28-day cycle: * Encorafenib: 300 mg (4 × 75 mg oral capsule) daily (QD) * Binimetinib: 45 mg (3 × 15 mg oral tablet) twice daily (BID) * Cetuximab: 500 mg/m2 every 2 weeks as per standard institutional practice.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)
Madrid, Spain

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06207656), the sponsor (Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06207656 clinical trial studying?

As a result of the little benefit obtained from standard treatments and the poor prognosis of these patients, the BRAF-V600E mutant MSS aCRC represents an unmet medical need requiring clinical research. The combination of encorafenib, cetuximab and binimetinib as second- or third-line treatment for mCRC resulted in significantly better outcomes than standard therapy in a phase 3 clinical trial, which also revealed treatment safety and tolerability to be acceptable. Compared to the control group (cetuximab and irinotecan or cetuximab and FOLFIRI), the triplet therapy cohort showed higher media… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06207656?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06207656?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06207656. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06207656. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.