Glumetinib Combined With Fruquintinib in the Treatment of MET Amplification or Protein Overexpression in Third-Line Unresectable Metastatic Colorectal Cancer

NCT06980532 | Recruiting Phase 1

• 1 other identifier: TJ-IRB202502131
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Glumetinib combined withFruquintinib in the treatment of MET amplification or protein overexpression in third-line unresectable metastatic colorectal cancer: evaluation of efficacy and safety

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Recommended dose for Phase II

  The dose determined during dose-escalation trials for use in Phase II studies, typically based on safety and tolerability data.

  Up to approximately 18 Weeks

• Objective response rate(ORR)

  In the phase II study,CR + PR rate according to the RECIST version 1.1 guidelines.

  Up to approximately 18 Weeks

Secondary Outcomes (7)

• Maximum tolerated dose(MTD)

  Up to approximately 18 Weeks

• Dose-limiting toxicity（DLT）

  Up to approximately 18 Weeks

• Assess Adverse Events

  up to 12 months

• Disease control rate（DCR）

  Up to approximately 18 Weeks

• Overall Survival (OS)

  Up to approximately 36 Months

Study Arms (1)

Glumetinib combined with Fruquintinib

EXPERIMENTAL

Drug: Glumetinib Combined with Fruquintinib

Interventions

Glumetinib Combined with Fruquintinib DRUG

Fruquintinib: 3mg, po.qd, d1-14，q3w; Guemitinib: Grade 1:200mg, po, qd, q3w; Grade 2:250mg, po, qd, q3w; Phase I: The dose of Glumetinib (200 mg → 250 mg) is dynamically adjusted using the "3+3 dose-escalation rule" to determine the optimal dose of Fruquintinib. Phase II: The RP2D (Recommended Phase II Dose) of Glumetinib identified in Phase I is continued in combination with Fruquintinib.

Glumetinib 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:

• The patients fully understood this study, voluntarily participated and signed the Informed Consent Form (ICF);
• Age ≥18 years old;
• Patients with unresectable metastatic colorectal cancer with microsatellite stable (MSS) confirmed by pathology or histology;
• Have MET amplification (FISH MET GCN≥4 or MET/CEP7≥1.8; Or NGS, ≥20% of tumor cells, ≥200X sequencing depth, GCN≥4) or overexpression (IHC, 3+(≥50% of tumor cells are strongly positive) or 2+ (≥50% of tumor cells are moderately positive/strongly positive and \< 50% of tumor cells are strongly positive); Immunohistochemistry (IHC) detection showed that the MET protein overexpression in the subjects was 3+(strongly positive in ≥50% of tumor cells) or 2+ (positive in ≥50% of tumor cells/weakly positive and strongly positive in \< 50% of tumor cells).
• Imaging confirmed progression after previous two-line standard anti-tumor regimens;
• According to RECIST1.1 criteria, the patient has at least one measurable target lesion; For lesions that have undergone radiotherapy in the past, they can only be included in measurable lesions when there is clear disease progression after radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) Physical Status Score: 0-1 point;
• The expected survival time is ≥3 months;
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥75×10\^9/L and hemoglobin 80 g/L, white blood cell count (WBC) ≥3.0×10\^9/L (corrected by no blood transfusion, no blood products, no use of granulocyte colony-stimulating factor or other hematopoietic stimulating factor within 14 days before laboratory tests);
• Liver and kidney functions: Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50mL/min; AST and ALT ≤2.5 times the upper limit of normal values (for patients with liver invasion, ≤5 times the upper limit of normal values); Serum total bilirubin ≤2 times the upper limit of normal value (for patients with liver invasion ≤2.5 times the upper limit of normal value);
• The activated partial thromboplastin time (APTT), International normalized ratio (INR), and prothrombin time (PT) are ≤1.5 times the normal upper limit value.
• Women of childbearing age must undergo a pregnancy test (serum) within 7 days before enrollment, with a negative result, and be willing to use appropriate contraceptive methods (such as intrauterine devices \[IUD\], contraceptives or condoms) during the test and 6 months after the last administration of the test drug; The serum pregnancy test must be negative within 7 days before enrollment in the study, and the subjects must be non-lactating. Male subjects who should agree that contraceptive measures must be adopted during the study period and within 6 months after the end of the study period;

You may not qualify if:

• Have received MET inhibitor treatment in the past; 2. Patients with unresectable metastatic colorectal cancer who have MSI-H/dMMR (MSI detection shows instability at two or more sites, and MMR detection shows loss of expression at any one protein); 3. Patients with unresectable metastatic colorectal cancer whose BRAF gene test is mutant and who have not received BRAF inhibitors /MEK inhibitors; 4. Patients with severe active bleeding, active peptic ulcers, unhealed gastrointestinal perforations, and peptic fistulas; 5. Have hypersensitivity reactions to any investigational drug or its components; 6. Concurrent severe and uncontrolled concurrent infections or other severe and uncontrolled concomitant diseases, moderate or severe renal injury; (such as progressive infection, uncontrollable hypertension, diabetes, etc.) 7. Infection during the active stage of hepatitis B and C (positive hepatitis B virus surface antigen and hepatitis B virus DNA exceeding 1 × 103 copies /mL; Hepatitis C virus RNA exceeds 1 × 103 copies /mL; 8. Human immunodeficiency virus (HIV) infection (HIV antibody positive); 9. Have had or are currently suffering from other malignant tumors simultaneously (except for effectively controlled non-melanoma basal cell carcinoma of the skin, breast/cervical carcinoma in situ, and other malignant tumors that have been effectively controlled without treatment in the past five years); 10. Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures; 11. Those with other malignant tumors requiring treatment; 12. The researchers judged that patients were not suitable to participate in this study.

Sponsors & Collaborators

• Liu Huang: lead

Study Sites (1)

Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

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

Xianglin Yuan, PhD,MD

CONTACT

13667241722; Xlyuan1020@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• 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 13, 2025
• First Posted: May 20, 2025
• Study Start: April 25, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)