US-based Verastem has started an open-label, dose escalation and schedule finding Phase I trial of a dual mTORC1/2 and PI3K inhibitor ‘VS-5584’ for treatment of patients with advanced solid tumours or lymphoma.
A total of 62 patients will be enrolled in the Phase I trial, which is aimed at evaluating the safety, pharmacokinetics, pharmacodynamics and initial clinical activity of single agent VS-5584.
The initiation is based on data from a preclinical research presented by the company on the ability of VS-5584 to preferentially target cancer stem cells.
Results of the preclinical research show that VS-5584 has equipotency against all four human Class I PI3K isoforms and both the mTORC1 and mTORC2 complexes of the mTOR kinase.
In the preclinical research, VS-5584 also decreased cancer stem cells across multiple in vitro and in vivo cancer models including triple negative breast cancer, small cell lung cancer and ovarian cancer.
Verastem chief medical officer Joanna Horobin said initiation of the clinical development of VS-5584 is an important milestone for the company.
"We are conducting this study with clinical investigators who have extensive experience with PI3K and mTOR inhibitors and applying our expertise in cancer stem cell biology to progress the development of the compound," Horobin said.
Recent research also showed that the dual inhibition of both PI3K and mTOR may be needed to reduce the observed resistance to PI3K-selective inhibitors in solid tumours.
Verastem president and chief executive officer Robert Forrester said start of the Phase I trial for VS-5584 marks the third compound into the clinic and sixth clinical trial that the company started this year.
"We have made significant progress in the development of novel drugs targeting cancer stem cells and we continue to work diligently towards our goal of bringing new treatment options for patients," Forrester said.
The company expects that additional clinical data from these trials will be made available in 2014.
In preclinical studies, VS-5584 has been demonstrated to reduce the percentage of cancer stem cells and induce tumour regression in multiple tumour models.
Image: Hodgkin’s lymphoma, nodular lymphocyte predominant – high power view – H&E. Photo: courtesy of Gabriel Caponetti.