Efficacy and Safety of Tunlametinib Combination Therapy in the Treatment of Second-line and Above Metastatic Colorectal Cancer

Starting soon · Phase 2

Conditions studied: CRC (Colorectal Cancer), BRAF

In brief

This study investigated the efficacy and safety of Tunlametinib Combination Therapy in the Treatment of Second-line and Above Metastatic Colorectal Cancer.

Key facts

Study ID

NCT07714447

Run by

Sun Yat-sen University

People needed

91

Starts

2026-11-30

Expected to finish

2029-02-26

Last updated by the study team

2026-07-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥ 18 years of age, both genders.
• ECOG, 0-1.
• Patients with metastatic colorectal cancer confirmed by histology or cytology
• Previous genetic test results can determine the gene status (mutation or wild type) of the RAS/RAF/MEK/ERK pathway (MAPK pathway), and the results of genetic testing or immunohistochemical testing can confirm whether it is MSS/pMMR or MSI-H/dMMR (if MSI-H/dMMR has been treated with PD-1 antibody, only the A cohort (MEK inhibitor + EGFR monoclonal antibody cohort) can be screened; if MSI-H/dMMR has not been treated with PD-1 antibody, the B cohort (MEK inhibitor + EGFR monoclonal antibody + PD-1 monoclonal antibody cohort) can be screened; if BRAF V600E mutation is present, the B cohort or C cohort (MEK inhibitor + EGFR monoclonal antibody / BRAF inhibitor + PD-1 monoclonal antibody cohort) can be screened).
• Patients were required to have at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• Previous treatment with at least one line of standard therapy failed (disease progression or intolerable side effects), and the patient is scheduled to receive ≥ 2 lines of treatment; for neoadjuvant or adjuvant therapy (chemotherapy or chemoradiotherapy), if disease progression occurs during treatment or within 6 months after discontinuation of treatment, it should be counted as the first line of treatment (assessed by the investigator according to RECIST 1.1);
• The life expectance should be at least 3 months.
• To ensure eligibility, the following criteria must be met regarding major organ and bone marrow functions:
• . Hematological Parameters: A complete blood count must indicate hemoglobin levels of ≥90 g/L (with no blood transfusions administered within the preceding 14 days), an absolute neutrophil count of ≥1.5 × 10⁹/L, and a platelet count of ≥100 × 10⁹/L.
• . Liver Function: Liver function tests should reveal alanine aminotransferase (ALT) levels ≤2.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) levels ≤2.5 × ULN, total bilirubin levels ≤1.5 × ULN, and albumin levels ≥30 g/L. In cases where liver metastases are present, ALT and AST levels may be elevated to ≤5 × ULN, while total bilirubin must remain ≤1.5 × ULN.
• . Renal Function: Renal function should be assessed with serum creatinine levels ≤1.5 × ULN or a creatinine clearance, calculated using the Cockcroft-Gault formula, of >60 mL/min.
• . Cardiac Function: Cardiac assessment via echocardiography should indicate a left ventricular ejection fraction (LVEF) of ≥55%. Additionally, the corrected QT interval (QTcF) on electrocardiogram should be ≤480 ms, with creatine kinase (CK) levels ≤1 × ULN and troponin or high-sensitivity troponin levels ≤1 × ULN.
• . Coagulation Function: Coagulation parameters must include an international normalized ratio (INR) of ≤1.5 × ULN and activated partial thromboplastin time (APTT) of ≤1.5 × ULN.
• . Urinalysis: Urinalysis should demonstrate urine protein levels of <2+. If urine protein levels are ≥2+, a 24-hour urine protein quantification test is required. Patients with quantitative urine protein levels <1 g/24 h are considered eligible, while those with levels ≥1 g/24 h are ineligible. Furthermore, patients exhibiting urine protein levels ≥2+ who have not undergone quantitative testing are also excluded.
• Participants may administer it orally.
• Females of childbearing potential had to have a negative pregnancy test at enrolment and agree to use an approved contraceptive method during and for 3 months after the study. Males of childbearing potential agreed to use effective birth control or abstinence during the study and for 3 months after the last treatment.
• All the subjects read and signed the informed consent.
• Paraffin-embedded tissue blocks or ≥10 slides.

You may not qualify if…

• Researchers must consider contraindications when selecting treatment drugs, such as allergies to any drug component.
• subjects who have previously used the cohort's treatment drugs (EGFRi, MEKi, BRAFi, immunotherapy) are excluded from screening.
• Within 4 weeks before the first use of the drug, underwent major surgery (excluding biopsies and minor outpatient surgeries, such as the placement of vascular access) or experienced serious trauma;
• There is the presence of clinically symptomatic third space effusion (such as large pleural effusion or ascites) that cannot be controlled through drainage or other methods;
• Subjects with symptomatic or untreated brain metastases, leptomeningeal metastases, or spinal cord compression, except for the following conditions: asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain lesions, no need for corticosteroids or antiepileptic drug treatment, and imaging confirms stability of lesions for ≥4 weeks; for patients who have undergone stereotactic brain radiotherapy or surgical treatment, if there has been no disease progression in the brain for 3 months or more, they can be included;
• Impaired cardiac function or clinically significant cardiovascular diseases, including any of the following:
• Acute coronary syndrome occurring within 6 months prior to treatment initiation, including acute myocardial infarction, unstable angina, coronary artery bypass graft surgery, coronary angioplasty, and stent implantation;
• Symptomatic congestive heart failure (New York Heart Association [NYHA] class ≥ II); evidence of clinically significant arrhythmias and/or conduction abnormalities within 6 months prior to treatment initiation or currently;
• Poorly controlled hypertension (systolic blood pressure ≥ 150 and/or diastolic blood pressure ≥ 100 mmHg under medication control);
• Abnormalities in heart valve morphology recorded by echocardiography (≥ grade 2), Note: Patients with grade 1 heart valve morphology abnormalities (such as mild regurgitation/stenosis) are allowed to enroll, but patients with moderate valve thickening are prohibited from enrolling;
• History of congenital long QT syndrome; or taking medications known to prolong the QT interval and unable to ensure discontinuation during the study.
• A history of retinal diseases during the past or screening, such as: retinal vein occlusion (RVO), retinal artery occlusion, retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal capillary dilatation (Costs disease), retinal pigment epithelial detachment (RPED), etc.; presence of risk factors for RVO during screening (for example, uncontrolled glaucoma or high intraocular pressure, history of hyperviscosity or hypercoagulable syndromes); retinal diseases such as RPED.
• Interstitial lung disease or interstitial pneumonia, including patients with clinically significant radiation pneumonia (i.e., those affecting daily activities or requiring intervention treatment);
• Positive for human immunodeficiency virus (HIV) antibodies, positive for syphilis antibodies (Anti TP), positive for hepatitis C virus (HCV) antibodies and HCV RNA, positive for hepatitis B virus surface antigen (HBsAg) and HBV DNA (positive HBsAg requires further testing for HBV DNA, with HBV DNA ≥ 200 IU/ml or ≥ 10\^3 copies/ml).
• There is an active autoimmune disease or a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism [patients who can be controlled by thyroid hormone replacement therapy can be included]), the subject has a skin disease that does not require systemic treatment (such as vitiligo, psoriasis, alopecia), is on insulin treatment and has controlled type 1 diabetes, or had a complete remission in childhood and no further intervention is needed in adulthood can be included (patients with asthma requiring medical intervention with bronchodilators cannot be included).
• It is known that there is a history of acute or chronic pancreatitis within 6 months before the start of treatment.
• History of allogeneic bone marrow transplantation or organ transplantation.
• Within 2 weeks prior to the initial administration of the drug, there are uncontrolled active infectious diseases (e.g., requiring intravenous administration of antibiotics, antifungals, or antiviral medications), or unexplained fever >38.5°C occurs during the screening period / before the first dose of the drug.
• Incurable electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia detected through blood biochemical tests).
• Past or currently existing neuromuscular diseases related to elevated CK (such as inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, rhabdomyolysis syndrome).
• Venous or arterial thrombotic events that occurred within the first 6 months prior to the initial use of the drug, such as cerebrovascular accidents (including transient ischemic attacks, intracerebral hemorrhages, cerebral infarctions), deep vein thrombosis, and pulmonary embolism, etc..
• Symptoms of grade 3 bleeding as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) occurred within 4 weeks prior to the first use of the drug.
• Patients with a history of other malignant tumors in the past 5 years are excluded, except for those who have been completely cured of skin basal cell carcinoma or skin squamous cell carcinoma and cervical carcinoma in situ, and/or any malignant tumor patients who have been cured with no disease or who have been disease-free for at least 5 consecutive years.
• A clear history of neurological or psychiatric disorders, including epilepsy and dementia;
• Have received any of the following antitumor treatments prior to the initial study of drug administration (either on the market or in clinical trials): ① Antitumor immunotherapy within 3 weeks; ② Large molecular targeted antitumor therapy such as Bevacizumab within 3 weeks; ③ Chemotherapy or clearly antitumor traditional medicine within 2 weeks; ④ Small molecule targeted antitumor drug treatment within 2 weeks or within 5 half-lives (whichever is longer); ⑤ Subjects who have undergone palliative radiation therapy for bone metastasis within 2 weeks are excluded, but those who have received radiation treatment with an area of ≥30% of the bone marrow within 2 weeks are not allowed to be included;

Where it is running

• Sun Yat-sen University — Guangzhou, Guangdong, China

Full record on ClinicalTrials.gov

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