Drug intelligence / Profile preview

bevacizumab + everolimus + panobinostat

Development stage
Phase 1
Lead developer
Roche
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

A three‑drug cancer regimen combining the anti‑VEGF monoclonal antibody bevacizumab, the mTOR inhibitor everolimus, and the pan‑histone deacetylase (HDAC) inhibitor panobinostat. Mechanistically, bevacizumab neutralizes VEGF‑A to inhibit angiogenesis; everolimus inhibits mTORC1 signaling to reduce tumor cell growth, proliferation, and angiogenesis; and panobinostat inhibits HDACs, affecting transcription, inducing apoptosis, and modulating hypoxia/angiogenesis pathways including HIF‑1α and VEGF signaling. A dedicated phase I study in advanced solid tumors found that the triplet at the lowest proposed doses did not have acceptable safety/tolerability, and no recommended phase II dose was established; overlapping toxicities included fatigue, thrombocytopenia, mucositis, hypertension, bleeding, and others.

Other names
bevacizumab and everolimus and panobinostatbevacizumab plus everolimus plus panobinostat
02

Targets

FKBP1AHDAC1 (Histone Deacetylase 1)HDAC2 (Histone deacetylase 2)HDAC3 (Histone Deacetylase 3)HDAC6 (Histone deacetylase 6)VEGFA (Vascular endothelial growth factor A)mTOR (Mammalian target of rapamycin kinase)

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