Immunotherapy company Aduro Biotech has dosed the first patient in a Phase l trial of ADU-S100 (MIW815), a new stimulator of interferon genes (STING) pathway activator, to treat cutaneously accessible tumours.
Activation of the STING pathway in tumours has proven to be a critical step to initiate an innate response that could lead to a systemic, adaptive, tumour-specific, immune response.
The Phase l, multicentre, dose escalation study includes dose expansion into designated indications and will enrol patients with cutaneously accessible, metastatic-solid tumours or lymphomas who are in need of other treatment alternatives.
The trial is conducted by Novartis, Aduro's collaborator for STING pathway activator compounds in oncology, and is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of ADU-S100.
The Aduro-proprietary, STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators designed to target and activate human STING.
STING is generally expressed at high levels in immune cells, such as dendritic cells.
When activated, the STING receptor begins a deep innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines.
This ultimately leads to the development of a systemic tumour, antigen-specific, T-cell adaptive, immune response.
Aduro noted that in preclinical models, direct activation of the STING pathway through intratumoral administration of ADU-S100 overcame immune system suppression within the tumour micro-environment, resulting in significant anti-tumour response.
Aduro Biotech chief scientific officer Thomas Dubensky said: "ADU-S100 is the first compound to enter the clinic under our collaboration with Novartis, and through this Phase l study, we look forward to gaining insight into the safety, tolerability and initial efficacy for several different types of cancer.
"We have now advanced two differentiated immuno-oncology platforms into the clinic: ADU-S100, with the start of this trial, and our LADD, listeria-based, immunotherapy strains in clinical studies in multiple indications, including pancreatic, ovarian, lung and prostate cancers, mesothelioma and glioblastoma."