Drug intelligence / Profile preview

AMG 655 + vorinostat

Development stage
Phase 1
Lead developer
Amgen
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous (amg 655), Oral (vorinostat)
01

Overview

AMG 655 + vorinostat is a **combination therapy** comprised of AMG 655, a fully human monoclonal antibody agonist that selectively binds and activates Death Receptor 5 (DR-5, also known as TRAIL receptor-2), and vorinostat, a histone deacetylase (HDAC) inhibitor. AMG 655 induces apoptosis in sensitive tumor cells by activating caspases through DR-5 signaling, while vorinostat alters chromatin structure and gene expression via inhibition of histone deacetylases. The rationale for combination is based on the synergistic pro-apoptotic effect: HDAC inhibitors like vorinostat sensitize tumor cells to TRAIL receptor agonists such as AMG 655, enhancing apoptosis for greater anti-tumor activity. This combination has been investigated in phase 1b trials for relapsed/refractory lymphoma and related hematological malignancies[1][5]. - **AMG 655** developed as a targeted immunotherapy for solid and hematologic cancers[2][5]. - **Vorinostat** is an FDA-approved HDAC inhibitor for cutaneous T-cell lymphoma, often used in investigational combinations for antineoplastic effects[5].

Other names
AMG 655 plus vorinostatAMG655 plus vorinostatAMG-655 plus vorinostatAMG655 + SAHA
02

Targets

TNFRSF10B (DR5)HDAC1 (Histone Deacetylase 1)HDAC2 (Histone deacetylase 2)HDAC3 (Histone Deacetylase 3)HDAC6 (Histone deacetylase 6)

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