A Single-arm, Multicenter Clinical Study of Fruquintinib Combined With Serplulimab and Chemotherapy as First-line Treatment for Patients With RAS/BRAF-mutated Advanced Colorectal Cance

This study is a prospective, single-arm, multicenter exploratory clinical study aimed at evaluating the efficacy and safety of Fruquintinib combined With Serplulimab and chemotherapy as first-line treatment for RAS/BRAF-mutated unresectable advanced colorectal cancer. The study plans to enroll 80 patients with RAS/BRAF-mutated unresectable advanced metastatic colorectal cancer. After evaluation and confirmation of meeting enrollment criteria, patients will receive treatment with Fruquintinib combined With Serplulimab and chemotherapy . The primary endpoint of the study is PFS, and secondary endpoints include ORR, DCR, OS, and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: Serplulimab+Fruquintinib+XELOX

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liang'jun Zhu; Phone Number: 13505199123; Email: zhulj98@foxmail.com

Study Locations

• China
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • The First People's Hospital of Changzhou
    • Changzhou, Jiangsu, China, 213000
      • Changzhou Tumor Hospital (Changzhou Fourth People's Hospital)
      • Contact: Yong Liu; Phone Number: 13921033137
    • Changzhou, Jiangsu, China, 213000
      • Liyang People's Hospital
      • Contact: Liqun Zhu; Phone Number: 13626255262
    • Huai'an, Jiangsu, China, 223000
      • Huaian First People's Hospital
      • Contact: Xiaomin Zhong; Phone Number: 13912074971
    • Lianyungang, Jiangsu, China, 222000
      • The First People's Hospital of Lianyungang
    • Nanjing, Jiangsu, China, 210000
      • First Affiliated Hospital of Nanjing Medical Unviersity
      • Contact: Jing Sun; Phone Number: 13914704178
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Cancer Institute & Hospital
      • Contact: Liang'jun Zhu; Phone Number: 13505199123; Email: zhulj98@foxmail.com
    • Nantong, Jiangsu, China, 226000
      • Nantong University Cancer Hospital
      • Contact: Lei Yang; Phone Number: 158 5139 8092
    • Nantong, Jiangsu, China, 226000
      • The First People's Hospital of Nantong
      • Contact: Liang zhang; Phone Number: 137 0629 5558
    • Suzhou, Jiangsu, China, 215000
      • Suzhou Municipal Hospital
      • Contact: jianming Shi; Phone Number: 138 1525 9001
    • Suzhou, Jiangsu, China, 215000
      • Changshu No.2 People's Hospital
      • Contact: Yulan Gu; Phone Number: 13812971602
    • Wuxi, Jiangsu, China, 214400
      • Jiangyin People's Hospital
      • Contact: Qiong Wang; Phone Number: 136 0616 8002
    • Wuxi, Jiangsu, China, 214000
      • Wuxi Huishan District People's Hospital
      • Contact: Ning Ding; Phone Number: 177 0617 8690
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou First People's Hospital
      • Contact: Taifeng Liu; Phone Number: 13685183529
    • Yangzhou, Jiangsu, China, 225000
      • Yangzhou University Affiliated Jiangdu People's Hospital
      • Contact: Min Liao; Phone Number: 15952578622
    • Yangzhou, Jiangsu, China, 225000
      • Yizheng People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 to 75 years (inclusive), male or female.
• Diagnosis of advanced unresectable or metastatic colorectal cancer.
• Confirmed RAS/BRAF mutation by testing.
• No prior systemic therapy for unresectable or metastatic colorectal cancer. (Prior adjuvant or neoadjuvant chemotherapy with one regimen is allowed if recurrence occurred ≥6 months after completion of chemotherapy.)
• ECOG 0 - 1.

• Adequate major organ and bone marrow function (without any blood component or cell growth factor support within 14 days before enrollment):

  1. Hematology: absolute neutrophil count ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, hemoglobin ≥90 g/L.
  2. International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN), and activated partial thromboplastin time (APTT) ≤1.5 × ULN.
  3. Liver function: total bilirubin ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (≤5 × ULN in patients with liver metastases).
  4. Renal function: serum creatinine ≤1.5 × ULN, and creatinine clearance (CCr) ≥50 mL/min.
• Female patients of childbearing potential must have a negative serum pregnancy test within 14 days before treatment. Fertile patients (male and female) must agree to use reliable contraceptive methods (hormonal, barrier, or abstinence) with their partners during the study and for at least 6 months after the last dose

Exclusion Criteria:

• - History of hypersensitivity to any anti-angiogenic targeted agent, any component of monoclonal antibodies, capecitabine, oxaliplatin, or other platinum-based drugs.
• Untreated central nervous system (CNS) metastases.
• Major surgery or severe trauma within 4 weeks prior to first study drug administration.
• Current use of immunosuppressive agents, or systemic or absorbable local hormone therapy for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent), and continued use within 2 weeks before enrollment.
• Presence of any active autoimmune disease or history of autoimmune disease.
• History of other malignancies within the past 5 years, except for radically resected basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Known inherited or acquired bleeding/thrombotic tendency (e.g., hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.) or currently receiving thrombolytic or anticoagulant therapy.
• Currently active bleeding or significant bleeding tendency within 3 months (i.e., patients at high risk of bleeding).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fruquintinib Combined With Serplulimab and XELOX; This study consists of two phases: combination and maintenance therapy. combination therapy administration： After screening and enrollment, patients will receive a first-line combination regimen of fruquintinib, serplulimab, and XELOX for 6-8 cycles. Maintenance therapy administration: After completion of the combination therapy, subjects with a response assessment of CR, PR, or SD, , will enter the maintenance phase: Fruquintinib、Serplulimaband Capecitabine , until diseas progression, unacceptable toxicity, or voluntary withdrawal of informed consent NOTE: If lesions become resectable, surgical treatment should be performed.

Drug: Serplulimab+Fruquintinib+XELOX; combination regimen of fruquintinib, serplulimab, and XELOX for 6-8 cycles. The dosing schedule is as follows: Fruquintinib: 3 mg/day, QD, PO, daily for 21 days of each 28-day cycle Serplulimab: 4.5 mg/kg, D1, intravenous infusion, Q3W XELOX ：Oxaliplatin: 130 mg/m², intravenous infusion over 0-2 hours, D1, Q3W Capecitabine: 1000 mg/m², PO, BID, D1-14, Q3W Maintenance therapy administration: After completion of the combination therapy, subjects with a response assessment of CR, PR, or SD, , will enter the maintenance phase: Fruquintinib、Serplulimaband Capecitabine , until diseas progression, unacceptable toxicity, or voluntary withdrawal of informed consent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Progression-Free Survival（PFS）	The time from the start of treatment in cancer patients to the observation of disease progression or death from any cause	From enrollment to the end of treatment at 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Objective Response Rate（ORR）	CR+PR	From enrollment to the end of treatment at 18 months
Overall Survival（OS）	Time from enrollment to death from any cause	From enrollment to the end of treatment at 36 months
DCR	CR+PR+SD	From enrollment to the end of treatment at 24 months
AEs	Safety analysis will be based on data from the safety population. It will primarily involve descriptive statistical analysis, with tables describing the adverse events that occurred in this study.	Through study completion, an average of 30 weeks

Collaborators and Investigators

• Sponsor: Jiangsu Cancer Institute & Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): August 15, 2028

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: RAS/BRAF-mutated
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: HMPL-013-FLAG-C133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No