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

Overview

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.

Interventions

• 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, , wil

Primary outcome measures

• Investigator-assessed Progression-Free Survival（PFS） [Time frame: From enrollment to the end of treatment at 18 months]

Secondary outcome measures (4)

• Investigator-assessed Objective Response Rate（ORR） [Time frame: From enrollment to the end of treatment at 18 months]
• Overall Survival（OS） [Time frame: From enrollment to the end of treatment at 36 months]
• DCR [Time frame: From enrollment to the end of treatment at 24 months]
• AEs [Time frame: Through study completion, an average of 30 weeks]

Eligibility criteria

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):

• Hematology: absolute neutrophil count ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, hemoglobin ≥90 g/L.
• International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN), and activated partial thromboplastin time (APTT) ≤1.5 × ULN.
• Liver function: total bilirubin ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (≤5 × ULN in patients with liver metastases).
• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 16 centers

• Changzhou Tumor Hospital (Changzhou Fourth People's Hospital) — Changzhou
• Liyang People's Hospital — Changzhou
• The First People's Hospital of Changzhou — Changzhou
• Huaian First People's Hospital — Huai'an
• The First People's Hospital of Lianyungang — Lianyungang
• First Affiliated Hospital of Nanjing Medical Unviersity — Nanjing
• Jiangsu Cancer Institute & Hospital — Nanjing
• Nantong University Cancer Hospital — Nantong
• … and 8 more centers

Identifiers

NCT: NCT07622550 · HMPL-013-FLAG-C133

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗