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sintilimab + oxaliplatin + 5-fluorouracil + nab-paclitaxel + lenvatinib

Development stage
Unknown
Lead developer
Innovent Biologics
Modality
Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules, Monoclonal Antibodies → Antibody-Based Therapeutics, Recombinant Proteins and Enzymes
Administration
Intravenous, Oral
01

Overview

This is a multi-agent combination regimen consisting of five drugs with distinct mechanisms of action, used primarily in investigational settings for advanced solid tumors such as intrahepatic cholangiocarcinoma (iCCA), combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and advanced gastric cancer. - Sintilimab is a fully human IgG4 monoclonal antibody that targets programmed cell death protein 1 (PD-1), blocking its interaction with ligands to enhance T-cell mediated anti-tumor immunity[6][8][9][10]. - Oxaliplatin is a platinum-based chemotherapeutic agent that induces DNA crosslinking and apoptosis in rapidly dividing cells. - 5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic that inhibits thymidylate synthase, disrupting DNA synthesis and repair. - Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) stabilizes microtubules, inhibiting mitosis and promoting apoptosis; it also enhances tumor antigen release and immune infiltration[2]. - Lenvatinib is an oral multikinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptor alpha, RET, and KIT, thereby inhibiting angiogenesis and tumor proliferation[1][2]. This combination aims to synergistically target the tumor through immune checkpoint inhibition, cytotoxic chemotherapy, microtubule disruption, and antiangiogenic effects.

02

Targets

DNAFGFR1 (Fibroblast growth factor receptor 1)FGFR2 (Keratinocyte growth factor receptor)FGFR3 (Fibroblast growth factor receptor 3)FGFR4 (Fibroblast growth factor receptor 4)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDCD1 (Programmed cell death protein 1 receptor)PDGFRA (Platelet-derived growth factor receptor alpha)RET (Rearranged during transfection receptor tyrosine kinase)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)FGFR (FGFR family)TUBB (Tubulin (alpha and beta subunits))

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