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The first-in-human PhAST trial, evaluating safety and effects of a selective N-glycosylation inhibitor, has started dosing the first patients in Milan and Montpellier
The dosing of the first three patients in the Dose Escalation phase of the PhAST trial, a Phase I/II study in patients with advanced solid tumors evaluating the First-In-Class selective N-glycosylation inhibitor PhOx430, has been announced today. The study is sponsored by Phost’In Therapeutics, a french biotechnology company founded in 2014 as concretization of ten years of academic works, and led by a consortium of clinician and researchers in Montpellier and Paris, with the scientific contribution of Gianni Bonadonna Foundation, which collaborated in the conception and design of the research protocol. PhAST trial aims to investigate for the first time the safety and pharmacokinetics effects of an N-glycosilation inhibitor in patients with advanced solid tumors, with a preliminary evaluation of efficacy and identification of biomarkers.
Glyco-immuno-oncology aberrant glycosylation of cancer cells is now recognized as a new immune checkpoint: the process modifies membrane proteins and also seems to contribute to ‘masking’ cancer cells from the immune system via the formation of complex abnormal glycan patterns operating as a shield. PhOx430 targets this aberrant glycosylation directly to the source through selective inhibition of a specific enzyme for a double antitumor effect, inducing simultaneously an anti-cancer immune response and the down regulation of the main receptors implicated in cancer. N-glycosilation inhibition has demonstrated a significant antitumoral efficacy in several animal models, associated with a promising safety profile in regulatory preclinical studies. Now the first three patients have been enrolled for the PhAST trial at the I.R.C.C.S. Ospedale San Raffaele in Milan, Italy, and at the Institute of Cancer of Montpellier, France: Diego Tosi, Gianni Bonadonna Foundation’s scientific coordinator and head of the Early Clinical Trial Unit – Medical Oncology Department of the Cancer Institute of Montpellier, has been entrusted with the international direction of this first-in-human clinical trial. The current dose escalation phase will enroll two dozen of patients with non-selected tumor types and it will be followed by three expansion cohorts gathering patients with selected tumor types, including Glioblastoma multiforme, Triple-negative breast cancer and a selection of other solid tumor types, for which few therapeutic options exist. «With the activation of both Sites involved in the Dose Escalation Phase a further step has been taken in this innovative first-in-human clinical trial, that could open new avenues for solid tumors therapy» Dr. Luca Gianni, President of The Gianni Bonadonna Foundation, said «With this in mind, Fondazione Gianni Bonadonna will continue collaborating with the PhAST Trial Team to achieve the best results for cancer patients’ benefit».