Drug intelligence / Profile preview

tislelizumab + pembrolizumab + pemetrexed

Development stage
Unknown
Lead developer
West China Hospital of Sichuan University
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Intrathecal
01

Overview

This combination refers to a therapeutic regimen being evaluated by the **West China Hospital of Sichuan University** for the treatment of **leptomeningeal metastases** (LM) in patients with **non-small cell lung cancer** (NSCLC). The regimen involves the administration of a programmed cell death protein 1 (PD-1) inhibitor—specifically either **tislelizumab** or **pembrolizumab**—in conjunction with **pemetrexed**, which is typically administered via intrathecal injection. Tislelizumab and pembrolizumab are monoclonal antibodies that block the PD-1 receptor on T-cells, preventing its interaction with ligands PD-L1 and PD-L2, thereby restoring anti-tumor immune responses. Pemetrexed is a folate antimetabolite that inhibits multiple enzymes involved in DNA synthesis, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). The combination aims to leverage systemic immunotherapy to control the primary tumor while using localized intrathecal chemotherapy to directly address central nervous system involvement, bypassing the blood-brain barrier.

Other names
PD-1 inhibitor + pemetrexed
02

Targets

TS (Thymidylate synthase)PDCD1 (Programmed cell death protein 1 receptor)DHFR (Dihydrofolate reductase)GART (GAR transformylase)

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