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

NCT07714447 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT-085-CRC-021
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

CRC (Colorectal Cancer); BRAF

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Defined as the percentage of subjects achieving complete response (CR) or partial response (PR) as assessed by RECIST 1.1.

  up to 180 days

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  up to 180 days

• Disease Control Rate (DCR)

  up to 180 days

• Duration of Response (DoR)

  up to 180 days

• Overall Survival (OS)

  up to 360 days

• Incidence and severity of adverse events (AEs)

  30 Days, an average of 3 months

Other Outcomes (1)

• Mechanism Exploration

  up to 720 days

Study Arms (3)

Tunlametinib + Cetuximab β Injection

EXPERIMENTAL

Tunlametinib: 9 mg per dose, administered orally twice daily (BID).The dosage of cetuximab β injection is 400mg/m2 for the first administration, and 250mg/m2 for subsequent administrations, administered by intravenous drip.

Drug: Arm1

Tunlametinib + Cetuximab β+Tislelizumab

EXPERIMENTAL

Tunlametinib: 9 mg per dose, administered orally twice daily (BID). Cetuximab β Injection: 500 mg/m² per dose (calculated based on body surface area), followed by 250 mg/m2, administered intravenously, once a week; Tislelizumab was administered intravenously at 200 mg every 3 weeks.

Drug: Arm 2

Tunlametinib + BRAF inhibitor + Tislelizumab

EXPERIMENTAL

Tunlametinib: 9 mg per dose, administered orally twice daily (BID). BRAF inhibitors (encorafenib, vemurafenib, dabrafenib, etc.) are selected by researchers from the available drugs based on their accessibility; Tislelizumab was administered intravenously at 200 mg every 3 weeks.

Drug: Arm 3

Interventions

Arm1 DRUG

Tunlametinib + Cetuximab β Injection

Tunlametinib + Cetuximab β Injection

Arm 2 DRUG

Tunlametinib + Cetuximab β+Tislelizumab

Tunlametinib + Cetuximab β+Tislelizumab

Arm 3 DRUG

Tunlametinib + BRAF inhibitor + Tislelizumab

Tunlametinib + BRAF inhibitor + Tislelizumab

Eligibility Criteria

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

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.

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).

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

26S proteasome non-ATPase regulatory subunit 13; DMAC2L protein, human

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Feng Wang MD, PhD

CONTACT

+86 020 87343795; wangfeng@sysucc.org.cn

Ming-ming He MD

CONTACT

hemm@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the medical department

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): November 30, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 26, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)