BeiGene Co, Ltd., an innovative oncology company focussed on developing targeted and immune-oncology therapeutics, has dosed the first patient in a phase 1 study of BGB-290 for the treatment of cancer. BGB-290 is an investigational, oral, selective and potent inhibitor of poly (ADP-ribose) polymerase (PARP), an enzyme family which is involved in a number of cellular processes, including DNA repair and programmed cell death.
BGB-290 is the second compound in BeiGene’s two-asset collaboration with Merck, which was established in 2013 with the goal of leveraging Merck’s global oncology development and commercialisation expertise. The first compound, BGB-283, an investigational second-generation B-RAF inhibitor, entered a phase 1 study in November 2013.
“We are excited to begin dosing in the first-in-human trial of BGB-290, which we believe has the potential to be a new and better PARP inhibitor option for the treatment of cancer,” said John V Oyler, chief executive officer, of BeiGene. “We continue to execute on our clinical plan through this strategic collaboration with Merck as we advance both compounds through the clinic and work toward our mission of developing life-saving cancer therapeutics to treat the unmet medical needs of cancer patients.”
“I am very pleased to be involved in the clinical development of this exciting new investigational anti-cancer drug,” commented Dr Michael Millward, lead investigator for the trial and Cancer Council Professor of Clinical Cancer Research at the University of Western Australia. “We are hopeful that BGB-290 will demonstrate the potential to offer significant advantages over other drugs in this class, and could become an important part of the treatment options for patients with common cancers including small cell lung cancer, gastric cancer, primary brain tumors, and some ovarian and breast cancers.”
The phase 1 multicentre, open-label, dose escalation clinical trial of BGB-290 is designed to assess the safety, tolerability and pharmacokinetic properties of BGB-290 as a single agent. Key objectives in the study include determining maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of BGB-290. Disease-specific expansion cohorts will be enrolled at the maximally-tolerated or biologically-relevant dose.
PARP proteins are involved in DNA replication, transcriptional regulation and DNA damage repair. Inhibition of PARP converts common single-strand DNA breaks into double-strand breaks during DNA replication. Small-molecule inhibitors of PARP1/2 represent a class of anticancer agents that exert their cytotoxic effect by modulating the PARylation activity of PARP1/2 and trap PARP proteins on damaged DNA. A number of PARP inhibitors have demonstrated sustained antitumour responses as a single agent in patients with BRCA1- or BRCA2-mutant tumours with good safety profiles.