Drug intelligence / Profile preview

lenalidomide + topotecan

Development stage
Discontinued
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Oral, Intravenous
01

Overview

**Lenalidomide + topotecan** is an investigational combination therapy pairing lenalidomide, an immunomodulatory and anti-angiogenic small molecule, with topotecan, a topoisomerase I inhibitor, aiming to treat advanced or recurrent epithelial ovarian or primary peritoneal carcinoma. Lenalidomide acts by inhibiting factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF)-alpha, contributing both direct tumoricidal and immunomodulatory effects. Topotecan inhibits DNA topoisomerase I, causing DNA damage and cell death, especially in rapidly proliferating cancer cells. Combination therapy was studied to capitalize on additive or synergistic effects, particularly anti-angiogenic normalization of tumor vasculature to enhance chemotherapy delivery. In clinical studies, the combination was discontinued in early phase trials due to excessive dose-limiting hematological toxicity, particularly severe neutropenia and thrombocytopenia, precluding the determination of a safe therapeutic dose[1].

Other names
lenalidomide + topotecan
02

Targets

FGF2TOP1 (DNA Topoisomerase I)VEGFA (Vascular endothelial growth factor A)TNFA (Tumor necrosis factor alpha (soluble))ICAM1 (Intercellular Adhesion Molecule 1)CRBN (Cereblon)IKZF3 (Zinc finger protein Aiolos)IKZF1 (Ikaros family zinc finger protein 1)LFA-1 (Integrin αLβ2)

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