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pexastimogene devacirepvec + sorafenib

Development stage: Discontinued
Lead developer: SillaJen
Modality: Small Molecules, Oncolytic Viruses → Oncolytic Therapeutics
Administration: Intratumoral, Intravenous, Oral

Overview

Pexastimogene devacirepvec + sorafenib is a combination therapy for advanced hepatocellular carcinoma (HCC). Pexastimogene devacirepvec (Pexa-Vec, JX-594) is a vaccinia virus-based oncolytic immunotherapy engineered to selectively infect and lyse tumor cells while expressing GM-CSF to stimulate anti-tumor immune responses. Sorafenib is a small-molecule multikinase inhibitor that blocks tumor cell proliferation and angiogenesis. The combination was investigated in the PHOCUS phase 3 trial as sequential therapy: pexastimogene devacirepvec administered intratumorally, followed by oral sorafenib. The approach aimed to leverage both direct oncolysis/immunogenicity (Pexa-Vec) and targeted kinase inhibition (sorafenib), but failed to demonstrate improved overall survival compared to sorafenib alone in first-line advanced HCC.

Brand names: Pexa-Vec + sorafenib
Other names: pexa-vec + sorafenibJX594 + sorafenib

Targets

CSF2R (Granulocyte-macrophage colony-stimulating factor receptor)BRAF (B-Raf proto-oncogene, serine/threonine kinase)FLT3 (Fms related receptor tyrosine kinase 3)PDGFRB (Platelet-derived growth factor receptor beta)RAF1 (c-Raf-1 (Y340D/Y341D))VEGFR3 (Vascular endothelial growth factor receptor 3)VEGFR2 (Vascular endothelial growth factor receptor 2)KIT (c-KIT proto-oncogene receptor tyrosine kinase)

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