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gemcitabine + cisplatin + lenvatinib + adebrelimab

Development stage
Phase 2
Lead developer
Nanfang Hospital, Southern Medical University
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
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Overview

This is a four-drug combination regimen consisting of gemcitabine, cisplatin, lenvatinib, and adebrelimab. - **Gemcitabine** is a nucleoside analog and antimetabolite chemotherapy agent that inhibits DNA synthesis by incorporating into DNA during replication, leading to cell death. It is commonly used in the treatment of various solid tumors including bladder cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, and biliary tract cancers[5][9]. - **Cisplatin** is a platinum-based chemotherapeutic that forms DNA crosslinks and induces apoptosis in rapidly dividing cells. It is widely used for multiple solid tumors such as bladder cancer, NSCLC, ovarian cancer, testicular cancer, and others[2][9]. - **Lenvatinib** is an oral small molecule multi-targeted tyrosine kinase inhibitor (TKI) that blocks vascular endothelial growth factor receptors (VEGFR1–3), fibroblast growth factor receptors (FGFR1–4), platelet-derived growth factor receptor alpha (PDGFRα), RET proto-oncogene (RET), and KIT proto-oncogene receptor tyrosine kinase. This results in inhibition of tumor angiogenesis and proliferation. - **Adebrelimab** is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). By blocking PD-L1 interaction with its receptor PD-1 on T cells, it enhances anti-tumor immune responses. This combination brings together cytotoxic chemotherapy agents with targeted therapy (lenvatinib) and immunotherapy checkpoint blockade (adebrelimab). The regimen aims to maximize anti-tumor efficacy through complementary mechanisms—direct cytotoxicity to tumor cells; inhibition of angiogenesis; and activation of the immune system against tumor cells.

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Targets

DNAKIT (c-KIT proto-oncogene receptor tyrosine kinase)CD274 (Programmed cell death protein 1 ligand 1)PDGFRA (Platelet-derived growth factor receptor alpha)RET (Rearranged during transfection receptor tyrosine kinase)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)FGFR2 (Keratinocyte growth factor receptor)RRM1

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