Fruquintinib Plus Anti-EGFR Antibody for Third-Line Treatment of RAS Wild-Type mCRC

NCT07724223 | Recruiting Phase 2 DMC

• 1 other identifier: NCCH0046
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the effectiveness and safety of combining fruquintinib (an oral anti-angiogenesis drug) with cetuximab-beta (an anti-EGFR antibody) in patients with RAS wild-type metastatic colorectal cancer who have already failed at least two lines of standard treatments. Standard therapies for metastatic colorectal cancer often include fluorouracil, oxaliplatin, and irinotecan. However, many patients eventually experience disease progression, and treatment options become limited. Fruquintinib and cetuximab-beta work through different mechanisms: fruquintinib blocks tumor blood vessel growth, while cetuximab-beta blocks EGFR-related cancer cell growth signals. Using these two drugs together may provide additional benefit for patients whose cancer no longer responds to other treatments. This study will enroll 46 patients who meet the eligibility criteria. All participants will take fruquintinib by mouth once daily (3 weeks on and 1 week off) and receive cetuximab-beta by intravenous infusion every 2 weeks. Treatment will continue until the cancer progresses or side effects become intolerable. Doctors will monitor tumor changes every 8 weeks using CT or MRI scans and will also collect blood samples over time to measure circulating tumor DNA (ctDNA), which may help track how the cancer responds to treatment. Safety will be assessed through physical exams, lab tests, and monitoring of side effects. The main goal of the study is to determine the objective response rate (ORR)-how many patients experience measurable tumor shrinkage. Secondary goals include progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety outcomes.

Conditions

Metastatic Colorectal Cancer (CRC)

Keywords

Metastatic Colorectal Cancer; RAS Wild-Type; Fruquintinib; Cetuximab-beta; Targeted Therapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of patients with a confirmed complete response or partial response using RECIST 1.1

  From the date of first study treatment until documented disease progression, initiation of a new anticancer therapy, or discontinuation of study treatment, whichever occurs first, up to 24 months.

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  From the date of first study treatment to the first documented disease progression or death from any cause, whichever occurs first, up to 24 months.

• Disease Control Rate (DCR)

  From the date of first study treatment until documented disease progression, initiation of a new anticancer therapy, or discontinuation of study treatment, whichever occurs first, up to 24 months.

• Overall Survival (OS)

  From the date of first study treatment to death from any cause, up to 36 months.

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

  From the first dose of study treatment through 90 days after the last dose, up to 24 months.

Other Outcomes (1)

• Circulating Tumor DNA (ctDNA)

  At baseline, every 8 weeks during study treatment, at documented disease progression, and 4-6 weeks after progression, up to 24 months after the first dose.

Study Arms (1)

Fruquintinib Plus Cetuximab-beta

EXPERIMENTAL

Drug: Fruquintinib plus Cetuximab-beta

Interventions

Fruquintinib plus Cetuximab-beta DRUG

Patients receive fruquintinib 5 mg orally once daily for 3 consecutive weeks followed by 1 week off in a 4-week cycle. Cetuximab-beta is administered intravenously at 500 mg/m² every 2 weeks. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Tumor assessments are performed every 8 weeks using RECIST 1.1 criteria. Safety is monitored through physical examinations, laboratory tests, vital signs, ECG, echocardiography, and adverse event reporting. Circulating tumor DNA (ctDNA) is collected at baseline, every 8 weeks during treatment, at progression, and 4-6 weeks after progression to evaluate molecular response and resistance dynamics. The regimen is designed for patients with metastatic colorectal cancer who previously failed standard fluoropyrimidine, oxaliplatin, and irinotecan-based therapies and who have RAS wild-type tumors.

Fruquintinib Plus Cetuximab-beta

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years, inclusive.
• Fully informed about the study and willing to sign written informed consent.
• Histologically confirmed metastatic or advanced colorectal adenocarcinoma.
• Tumor confirmed as NRAS, KRAS, and BRAF wild-type.
• At least one measurable lesion according to RECIST 1.1 criteria.
• ECOG performance status of 0-1.
• Estimated life expectancy ≥ 12 weeks.
• Prior treatment with oxaliplatin- and irinotecan-based therapy, or failure of at least two prior standard regimens.
• Prior treatments must have included fluoropyrimidine, oxaliplatin, and irinotecan (with or without bevacizumab or cetuximab).
• Treatment failure defined as disease progression during therapy or within 3 months after last treatment, or intolerance to toxicity.
• Recurrence within 6 months after adjuvant/neoadjuvant therapy is considered as first-line failure.
• Adequate organ function within 7 days prior to enrollment:
• ANC ≥ 1.5 × 10⁹/L
• Platelets ≥ 80 × 10⁹/L
• Hemoglobin ≥ 8 g/dL

You may not qualify if:

• Unable or unwilling to comply with the study protocol.
• Prior treatment with VEGFR tyrosine kinase inhibitors (e.g., regorafenib).
• Participation in another clinical trial within 4 weeks.
• Systemic anticancer therapy within 4 weeks before enrollment.
• Uncontrolled hypertension (SBP \> 140 mmHg or DBP \> 90 mmHg).
• Any condition that affects drug absorption or inability to take oral medication.
• Active gastric or duodenal ulcer, ulcerative colitis, or tumor-related active bleeding.
• Arterial or deep venous thrombosis within 6 months.
• Significant bleeding within 2 months (melena, hematemesis, hemoptysis).
• Stroke or transient ischemic attack within 12 months.
• Significant cardiovascular disease:
• Acute myocardial infarction within 6 months
• Severe or unstable angina
• Heart failure NYHA class \> II
• Clinically significant arrhythmia requiring treatment

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100021, 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

Study Officials

• Yongkun Sun

  National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongkun Sun

CONTACT

(+86)010-87788800; hsunyk@cicams.ac.cn

Qifan Wang

CONTACT

(+86)010-87788800; wqf10028@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 24, 2026
• Study Start: January 16, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: July 24, 2026

Record last verified: 2026-01

Locations

CN (1)