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ONCOS-102 + cyclophosphamide + durvalumab

Development stage
Unknown
Lead developer
Targovax
Modality
Small Molecules, Oncolytic Viruses → Oncolytic Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intratumoral, Intravenous, Oral
01

Overview

ONCOS-102 + cyclophosphamide + durvalumab is an investigational combination therapy for cancer, particularly solid tumors. The regimen combines three agents: - **ONCOS-102** is a genetically engineered oncolytic adenovirus (Ad5/3-D24-GMCSF) designed to selectively replicate in and destroy p16/Rb-defective tumor cells. It also expresses granulocyte–macrophage colony-stimulating factor (GM-CSF), which stimulates the immune system by recruiting and activating dendritic cells, leading to enhanced antigen presentation and T-cell activation[4][3][2]. - **Cyclophosphamide** is a well-established alkylating agent that suppresses regulatory T cells at low doses, potentially enhancing anti-tumor immune responses. - **Durvalumab** is a monoclonal antibody targeting programmed death-ligand 1 (PD-L1), functioning as an immune checkpoint inhibitor to restore anti-tumor T-cell activity. The rationale for this combination is that ONCOS-102 primes the tumor microenvironment by inducing immunogenic cell death and promoting infiltration of cytotoxic CD8+ T-cells[2][3]. Cyclophosphamide may further modulate the immune response by reducing immunosuppressive regulatory T-cells. Durvalumab blocks PD-L1-mediated inhibition of activated T-cells, allowing sustained anti-tumor immunity. This multi-modal approach aims to convert "cold" tumors into "hot" ones—making them more responsive to checkpoint blockade—and has shown promising safety and early efficacy signals in clinical studies with similar combinations[2][5].

Other names
Ad5/3-D24-GMCSF + cyclophosphamide + durvalumab
02

Targets

CSF2R (Granulocyte-macrophage colony-stimulating factor receptor)CD274 (Programmed cell death protein 1 ligand 1)DNARB1 (Retinoblastoma-associated Protein)

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