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fruquintinib + nivolumab + sintilimab + oxaliplatin + tegafur + gimeracil + oteracil + capecitabine

Development stage
Preclinical
Lead developer
HUTCHMED
Modality
DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Oral, Intravenous
01

Overview

This is a multi-agent **combination regimen** comprising seven distinct anticancer drugs with complementary mechanisms. - **Fruquintinib** is a small-molecule inhibitor targeting vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, thereby inhibiting tumor angiogenesis[2][4][5]. - **Nivolumab** is a monoclonal antibody that blocks programmed cell death protein 1 (**PD-1**), enhancing anti-tumor immune responses. - **Sintilimab** is also a monoclonal antibody targeting PD-1, with similar immune checkpoint inhibition action. - **Oxaliplatin** is a platinum-based chemotherapy agent that forms DNA cross-links, inhibiting DNA synthesis and function. - **Tegafur, gimeracil, and oteracil** are combined as an oral prodrug formulation (often referred to as S-1 or similar) that delivers 5-fluorouracil (5-FU) systemically: tegafur is converted to 5-FU, gimeracil inhibits 5-FU degradation, and oteracil reduces gastrointestinal toxicity. - **Capecitabine** is an oral prodrug converted to 5-FU, acting as an antimetabolite chemotherapeutic agent inhibiting DNA synthesis. This regimen combines **antiangiogenic therapy, immune checkpoint blockade, and cytotoxic chemotherapy**. It is investigational as a specific combination; its components are indicated primarily for metastatic colorectal cancer and other solid tumors, but the combination itself is not an approved product.

02

Targets

DNAPDCD1 (Programmed cell death protein 1 receptor)TS (Thymidylate synthase)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)

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