Submitted to competent authorities an innovative clinical trial that could open new avenues for solid tumors therapy, introducing treatment strategies different from those known so far.
The study is sponsored by Phost’In Therapeutics, a 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.
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 in France, has been entrusted with the international direction of this first-in-human clinical trial, conducted in French and Italian Oncological Centers, and aimed to investigate the possibility of targeting tumors with a selective N-glycosylation inhibitor.
In the field 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. Hence the idea of using a selective N-glycosylation inhibitor for a double antitumor effect, inducing simultaneously the down regulation of the main receptors implicated in cancer and an anti-cancer immune response. «This is the first drug with this type of approach», Diego Tosi explains. «The antitumor action seems possible mostly thanks to the effect on the membrane receptors and seems to be able to reduce disease aggressiveness; there are less data on how the immune response is modified, but our research will try to find answers».
The clinical study protocol has been defined and patient recruitment is expected to begin in early 2022; in a first dose escalation phase 21 patients with solid tumors will be involved, then a second phase will enroll patients with specific tumors such as glioblastoma multiforme (GBM), triple negative breast cancer, for which few therapeutic options exist, and other solid tumors that will be selected by the Protocol Steering Committee after the conclusion of the dose escalation phase. The primary objective will be to determine the safety and tolerability of the drug, the secondary objectives will be the characterization of the pharmacokinetic profile and a preliminary evaluation of the potential efficacy, in addition to the identification of biomarkers useful for predicting and monitoring the patients clinical response. «Even if the drug production is simple, a scale-up is always complex, and we will need significant quantities of the inhibitor: there are some significant challenges, but this is a very interesting strategy to investigate», Tosi says.