On July 23, 2020 Quadriga BioSciences, a leader in the field of transporter technology for cancer therapeutics, reported that the first patient has been dosed in a Phase 1 study of QBS10072S in patients with advanced malignancies. QBS10072S is a novel, first-in-class, bifunctional amino acid analogue that targets LAT1 (L-type amino acid transporter 1) expressing cancers for active transport into tumor cells to disrupt DNA replication (Press release, Quadriga BioSciences, JUL 23, 2020, View Source [SID1234562311]). It is well-recognized that LAT1 is highly expressed on many aggressive forms of cancer and has been shown to be an independent prognostic factor of poor patient outcome. QBS10072S is designed to be transported into high LAT1 expressing tumor cells and spare normal tissues, which typically do not express LAT1.
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"Today’s announcement marks the initiation of the first-in-class LAT1 targeted cancer clinical program for the company," said Gordon Ringold, Ph.D., chief executive officer of Quadriga BioSciences. "Initiation of this study is a major milestone for Quadriga and our partner, NBQ, a joint venture of Quadriga in China, that has partnered with us on the development of QBS10072S. We believe this program has the potential to significantly help patients with brain metastases and those with late-stage astrocytoma, also known as glioblastoma multiforme (GBM)."
Preclinical studies have demonstrated that QBS10072S significantly suppresses tumor growth and improves survival in a triple negative breast cancer (TNBC) spontaneous brain metastasis model and in orthotopic GBM models. Additionally, whole body autoradiography studies with radiolabeled QBS10072S showed significant drug accumulation in the brain tumors of mice when the drug was administered intravenously.
"One of the biggest hurdles to developing effective treatments for brain cancer is that most drugs cannot cross the blood-brain-barrier (BBB), and it is encouraging to see the preclinical data of QBS10072S was able to be transported across the BBB, accumulate preferentially in the brain tumor, resulting in reduced tumor growth and improved survival in animal models," said Professor W. K. Alfred Yung, M.D., Professor of Neuro-Oncology at MD Anderson and executive committee member of the Moon Shots Program. "I look forward to the development of QBS10072S in patients with brain metastases and glioblastoma multiforme."
"We are very pleased to be in partnership with Quadriga BioSciences to advance this novel and important treatment into clinical development for central nervous system (CNS) cancers, for which very limited treatment options are available for patients," said Frank Yan, Ph.D., chief executive officer of NBQ and partner at 3E Bioventures Capital. "This research furthers the field of cancer metabolism and advances potential treatment options for patients whose cancers harbor genetic abnormalities."
About the Study
The Phase 1, multicenter, open-label, dose-escalation clinical trial is designed to assess the safety and tolerability of QBS10072S in patients with various metastatic malignancies. The primary objectives of the study are to determine the maximum tolerated dose, pharmacokinetics, and preliminary anti-tumor activity of QBS10072S. Disease-specific expansion cohorts with brain metastases and astrocytoma will be enrolled at the maximally tolerated or biologically relevant dose. Please refer to www.clinicaltrials.gov for additional clinical trial details.