A first-in-class small molecule with a novel mechanism of action that selectively induces cancer cell death is to undergo phase I clinical trials. Its makers, Cylene Pharmaceuticals have claimed the drug candidate has shown efficacy in colorectal, pancreatic, and prostate cancers.
CX-3543 represents a first-in-class quadruplex-interactive small molecule, designed to selectively interact with a particular class of quadruplex-forming nucleic acid structures relative to other classes of quadruplexes and other forms of DNA or RNA.
This targeted quadruplex interaction results in the activation of specific genomic surveillance pathways that trigger rapid and massive apoptotic cell death in tumour cells. Because of this novel mechanism, CX-3543 has the potential to act on a broad range of cancers.
It is a proprietary small molecule designed to selectively interact with quadruplex nucleic acid structures and induce apoptotic cell death in cancer cells.
Preclinical studies with CX-3543 have shown favourable pharmacokinetic properties, potent in vivo efficacy in murine xenograft models with a broad safety window, as well as practical formulation, stability and drug manufacturing properties.
The clinical trial is designed to enroll approximately 36 patients with solid tumours or lymphomas. The objectives of the trial are to determine the safety and tolerability of CX-3543, to characterise its pharmacokinetic profile, to define dose-limiting toxicities and the maximum-tolerated dose, and to select the appropriate dose for phase II trials.
"We're very gratified to advance CX-3543 into clinical trials," said William Rice, CEO of Cylene.
"The novel mechanism of this compound engenders the potential for treating many types of cancers, and CX-3543 has shown very favourable safety and efficacy profiles during preclinical testing," he added.
"CX-3543 has demonstrated a favourable in vivo safety profile, as well as compelling anti-tumour activity in xenograft models of colorectal, pancreatic, and prostate cancers," said Cylene co-founder Daniel Von Hoff.
Preclinical studies with CX-3543 demonstrated favorable pharmacokinetic and safety profiles, as well as compelling manufacturing, formulation and stability properties. Moreover, CX-3543 exerts potent in vivo antitumor efficacy against multiple types of human tumours in murine xenograft models with a broad safety window.
The phase I clinical trial of CX-3543 has been initiated at two centres in the US: the Institute of Drug Development at the Cancer Therapy and Research Centre in San Antonio, Texas, and at the Mayo Clinic Arizona in Scottsdale, Arizona.
In this phase I study, CX-3543 will be administered as a one-hour infusion once daily for five consecutive days, followed by two weeks and two days off therapy. Patients who successfully complete the three-week cycle without evidence of significant treatment-related toxicity or progressive disease will continue to receive CX-3543 doses.
A standard phase I dose escalation design will be used to identify the maximum tolerated dose (MTD), and 14 additional patients will be added at the MTD level to confirm safety.