An Exploratory Clinical Study Evaluating the Efficacy and Safety of Tunlametinib Combined With Fruquintinib in the Third-line Treatment of Advanced Colorectal Cancer Patients With RAS Mutations.

NCT06985316 | Not Yet Recruiting

• 1 other identifier: TJ-IRB202504032
• Study Type: interventional
• Target: 34
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a prospective, open-label, single-arm clinical study aimed at evaluating the efficacy and safety of Tunlametinib combined with Fruquintinib in the third-line treatment of advanced colorectal cancer patients with RAS mutations.

Conditions

CRC, Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progress Free Survival

  Time from treatment beginning until disease progression

  Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks

Secondary Outcomes (6)

• Objecitve response rate

  Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks

• Disease control rate

  Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks

• Duration of Response

  Through study completion, an average of 3 weeks

• Overall Survival

  From date of treatment beginning until the date of death from any cause, through study completion, an average of 3 weeks

• Incidence of Treatment-related adverse Events

  Through study completion, an average of 3 weeks

Study Arms (1)

Tunlametinib combined with Fruquintinib

EXPERIMENTAL

Drug: Tunlametinib combined with Fruquintinib

Interventions

Tunlametinib combined with Fruquintinib DRUG

Tunlametinib combined with Fruquintinib

Tunlametinib combined with Fruquintinib

Eligibility Criteria

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

You may qualify if:

• )18 years old or older, both males and females are allowed; 2)ECOG performance status of 0 or 1; 3)Histologically or cytologically proven advanced colorectal cancer; 4)Previous gene testing results indicate positive RAS mutation; 5)According to RECIST v1.1 assessment, there is at least one measurable lesion; 6)Patients who have previously failed second-line systemic antitumor therapy, and have imaging evidence of disease progression, or who are intolerant to the treatment regimen; patients who have failed front line immunotherapy are allowed to receive cross-line treatment; 7)Expected survival period \> 3 months; 8)The main organ functions and bone marrow function are normal, meeting the following requirements:
• Blood routine: Hemoglobin ≥80 g/L (no blood transfusion in the last 14 days); Absolute neutrophil count ≥1.5×10\^9/L; Platelet count ≥90×10\^9/L;
• Liver function: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) ≤2.5×upper limit of normal (ULN); if liver metastasis is present, ALT and AST ≤5×ULN, ALP ≤6×ULN; Total bilirubin ≤1.5×ULN; Albumin ≥30 g/L;
• Kidney function: Serum creatinine ≤1.5×ULN or creatinine clearance calculated by the Cockcroft-Gault formula \>60 mL/min;
• Heart function: Echocardiography shows left ventricular ejection fraction (LVEF) ≥55%; ECG QTcF ≤480ms; Creatine kinase (CK) ≤1×ULN, troponin/sensitive troponin ≤1×ULN;
• Coagulation function: International Normalized Ratio (INR) for prothrombin time ≤1.5×ULN; Activated partial thromboplastin time (APTT) ≤1.5×ULN;
• Urinalysis: Urine protein \<2; when ≥2, a 24-hour urine protein quantification test should be performed; if the quantification test \<1g/24h, they can be included in the group; if urine protein ≥1g/24h, they cannot be included; if urine protein ≥2 without quantification testing, they cannot be included; 9)Able to take oral medication; 10)Women of childbearing age must undergo a pregnancy test (serum or urine) within 14 days prior to enrollment, with negative results, and voluntarily use appropriate contraception during the observation period and for 3 months after the last administration of the study drug; for men, they should be surgically sterilized or agree to use appropriate contraception during the observation period and for 3 months after the last administration of the study drug; 11)Voluntarily participate and sign the informed consent form, expected to have good compliance and be able to cooperate with the study according to the protocol requirements.

You may not qualify if:

• There are contraindications that influence investigators' choices in the use of therapeutic drugs (according to the latest drug instructions).
• Previously received MEK inhibitors;
• 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);
• A history of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulators or surgery) within 12 months prior to the start of treatment;

Sponsors & Collaborators

• Liu Huang: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013

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

Liu Huang

CONTACT

13871312014; huangliu017@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 22, 2025
• Study Start: May 19, 2025
• Primary Completion (Estimated): April 27, 2028
• Study Completion (Estimated): April 27, 2028
• Last Updated: May 22, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share