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CRC (Colorectal Cancer)Phase 2NCT07714447

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

A Phase 2 study testing Arm1, Arm 2 and Arm 3 in people with CRC (Colorectal Cancer) and BRAF, run by Sun Yat-sen University at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
CRC (Colorectal Cancer), BRAF
What is being tested?
Arm1, Arm 2 and Arm 3
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
1 siteChina
Study dates
30 Nov 2026to 26 Feb 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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);
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  • 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.

Who cannot join

  • 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:
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  • 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;
  • Before studying drug administration, all related toxic reactions from antitumor treatments (such as hair loss, skin pigmentation, grade 2 chemotherapy-related peripheral neurotoxicity, grade 2 toxicities caused by immune checkpoint inhibitors like elevated blood sugar or hypothyroidism, etc.) have not recovered to a level of ≤ grade 1 (as determined by NCI CTCAE v5.0);
  • Patients may be used in conjunction with other anticancer drugs (bisphosphonates for the treatment of bone metastases are acceptable);
  • Uncontrolled comorbidities, including but not limited to severe diabetes (fasting blood glucose > 250 mg/dl or 13.9 mmol/L), or other severe diseases requiring systemic treatment;
  • Vaccination with live vaccines or attenuated vaccines within 4 weeks prior to the first dose (Note: If enrolled, participants must not receive live vaccines during the study treatment period and within 30 days after the last dose of the investigational drug);
  • For premenopausal female subjects (postmenopausal female patients must have been menopausal for at least 12 months to be considered infertile), a positive pregnancy test result; during the study and at least 30 days after the last administration of the study drug, females of childbearing potential who are hoping to become pregnant, breastfeeding, or unwilling to use effective contraceptive methods (including female partners of male subjects).
  • subjects who are undergoing treatment and cannot discontinue (for at least 1 week prior to study treatment initiation and during the study) any intravenous or oral medications that are strong inducers or strong inhibitors of CYP2C9 or CYP3A4; or patients who are taking medications with a narrow therapeutic window that are metabolized by CYP1A2.
  • Inability to swallow capsules or refractory nausea and vomiting, malabsorption, external bile diversion, or any significant small bowel resection that may interfere with the complete absorption of the study drug.
  • Any other condition or circumstance that, in the investigator's judgment, would preclude safe participation in or compromise the objectives of the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Feng Wang MD, PhD contact

+86 020 87343795

wangfeng@sysucc.org.cn

Ming-ming He MD contact

hemm@sysucc.org.cn

China1 site

  • Sun Yat-sen University

    Guangzhou, Guangdong, 510000

    Feng Wang MD, PhD, +86 020 87343795, wangzhq@sysucc.org.cn

Other trials in China

About this study

Official title: Efficacy and Safety of Tunlametinib Combination Therapy in the Treatment of Second-line and Above Metastatic Colorectal Cancer: a Multicentre, Multicohort, Phase 2 Trial.

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

Being tested
Arm1, Arm 2, Arm 3
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Arm1Drug

    Tunlametinib + Cetuximab β Injection

  • Arm 2Drug

    Tunlametinib + Cetuximab β+Tislelizumab

  • Arm 3Drug

    Tunlametinib + BRAF inhibitor + Tislelizumab

Study groups in NCT07714447
Study groupRoleWhat they receive
Tunlametinib + Cetuximab β InjectionExperimentalTunlametinib: 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.
Receives: Drug: Arm1
Tunlametinib + Cetuximab β+TislelizumabExperimentalTunlametinib: 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.
Receives: Drug: Arm 2
Tunlametinib + BRAF inhibitor + TislelizumabExperimentalTunlametinib: 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.
Receives: Drug: Arm 3

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 180 days

Secondary outcomes (5)

  1. Progression Free Survival (PFS)

    Defined as the time from randomization to the date of first documentation of from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.

    Measured: up to 180 days

  2. Disease Control Rate (DCR)

    DCR was defined as the proportion of CR+PR+SD subjects to total subjects

    Measured: up to 180 days

  3. Duration of Response (DoR)

    DoR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death.

    Measured: up to 180 days

  4. Overall Survival (OS)

    From date of randomization until the date of death from any cause

    Measured: up to 360 days

  5. Incidence and severity of adverse events (AEs)

    Overall incidence of AEs; the incidence of grade 3 or above AEs; the incidence of severe adverse events (SAE); the incidence of drug-related AEs; the incidence of AEs resulting in permanent withdrawal of drugs; the incidence of AEs leading to dose adjustment.

    Measured: 30 Days, an average of 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2026
  2. Study start30 Nov 2026 (estimated)
  3. Primary completion1 Feb 2029 (estimated)
  4. Study completion26 Feb 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
91 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07714447
Sponsor's protocol ID
IIT-085-CRC-021
Status last verified
Jul 2026
First submitted
15 Jul 2026
Last updated
21 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Arm1, Arm 2 and Arm 3 in people with CRC (Colorectal Cancer) and BRAF, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Feng Wang MD, PhD (+86 020 87343795, wangfeng@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: up to 180 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07714447.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.

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