NCT07446465

FOLFOX Chemotherapy Combined With Fruquintinib and Serplulimab as First-Line Conversion Therapy for Initially Unresectable pMMR/MSS Colorectal Cancer

Exploratory Clinical Study of FOLFOX Chemotherapy Combined With Fruquintinib and Serplulimab as First-Line Conversion Therapy for Initially Unresectable pMMR/MSS Colorectal Cancer

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Ye Xu · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

To evaluate the efficacy and safety of immune checkpoint inhibitor-based combination therapy with targeted therapy and chemotherapy in patients with locally advanced unresectable or metastatic colorectal cancer.

Detailed description

1.1 Overview of Colorectal Cancer Colorectal cancer (CRC) is the third most common malignancy worldwide and a leading cause of cancer-related mortality. In China, CRC incidence and mortality continue to rise, with a high proportion of patients diagnosed at advanced stages. While radical surgery remains the cornerstone of curative treatment, many patients present with unresectable disease, and long-term survival remains poor. Immune checkpoint inhibitors targeting PD-1/PD-L1 have transformed cancer therapy; however, their benefit in CRC is largely confined to dMMR/MSI-H tumors, which account for only 10-15% of cases. The majority of CRC patients with pMMR/MSS disease derive little benefit from immunotherapy alone. 1.2 Conversion Therapy in Colorectal Cancer Conversion therapy aims to downstage initially unresectable tumors through systemic treatment, enabling surgical resection. In metastatic CRC, successful conversion followed by radical resection can significantly improve long-term survival, with 5-year survival rates reaching 30-50% in selected patients. 1.3 Immunotherapy and Targeted Therapy in pMMR/MSS CRC pMMR/MSS tumors are considered "cold tumors" with low tumor mutational burden and limited immune cell infiltration. Multiple trials have shown minimal efficacy of PD-1 inhibitors alone in this population. Combination strategies incorporating chemotherapy and anti-angiogenic agents may enhance immune response and improve outcomes. 1.4 Serplulimab Serplulimab is a fully humanized anti-PD-1 IgG4 monoclonal antibody with high affinity, slow dissociation, low immunogenicity, and favorable safety characteristics. It has been approved in China for multiple indications including lung cancer and esophageal squamous cell carcinoma, with demonstrated survival benefits. 1.5 Fruquintinib Fruquintinib is a highly selective small-molecule VEGFR inhibitor targeting VEGFR-1, -2, and -3. It inhibits tumor angiogenesis with high potency and manageable toxicity. Fruquintinib has been approved for metastatic colorectal cancer refractory to standard therapies. 1.6 Rationale for This Study Based on strong preclinical and clinical evidence supporting the synergistic effects of immunotherapy, anti-angiogenic therapy, and chemotherapy, this study is the first to explore serplulimab combined with fruquintinib and FOLFOX chemotherapy as first-line conversion therapy in pMMR/MSS colorectal cancer.

Conditions

• Colorectal Cancer (Locally Advanced or Metastatic)
• Colorectal Cancer Microsatellite Stable (MSS)

Interventions

Type	Name	Description
DRUG	Serplulimab	Serplulimab: 200 mg IV Day 1, q2w
DRUG	Fruquintinib	Fruquintinib: 4 mg orally once daily, Days 1-21, every 4 weeks
DRUG	mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU)	Oxaliplatin 85 mg/m² IV q2w Leucovorin 400 mg/m² IV q2w 5-FU 400 mg/m² IV bolus Day 1 5-FU 1200 mg/m²/day continuous IV infusion Days 2-3

Timeline

• Start date: 2026-03-01
• Primary completion: 2027-01-31
• Completion: 2027-01-31
• First posted: 2026-03-03
• Last updated: 2026-03-03

Locations

1 site across 1 country: China