Drug intelligence / Profile preview

pemetrexed + cisplatin + carboplatin + bevacizumab + durvalumab + SBRT

Development stage
Unknown
Lead developer
AstraZeneca
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, External Beam Radiation Therapy
01

Overview

This combination regimen represents a multi-modal therapeutic approach primarily investigated for the treatment of advanced non-small cell lung cancer (NSCLC). It integrates cytotoxic chemotherapy (pemetrexed and platinum agents cisplatin or carboplatin), anti-angiogenic therapy (bevacizumab), and immunotherapy (durvalumab), often sequenced with stereotactic body radiation therapy (SBRT). Pemetrexed acts as an antifolate, inhibiting thymidylate synthase and other folate-dependent enzymes to disrupt DNA synthesis. Cisplatin and carboplatin are platinum-based agents that form DNA cross-links, inducing apoptosis. Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), inhibiting tumor angiogenesis. Durvalumab is a checkpoint inhibitor that targets programmed cell death ligand 1 (PD-L1), preventing its interaction with PD-1 and B7.1 to restore T-cell anti-tumor activity. SBRT is utilized to provide ablative doses of radiation to specific tumor sites, potentially inducing an abscopal effect and enhancing the efficacy of the systemic immunotherapy.

02

Targets

GART (GAR transformylase)VEGFA (Vascular endothelial growth factor A)CD274 (Programmed cell death protein 1 ligand 1)DHFR (Dihydrofolate reductase)ATIC (Aminoimidazole carboxamide ribonucleotide transformylase)TS (Thymidylate synthase)

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