BeiGene Co., Ltd., an innovative Chinese oncology R&D company, has enrolled first patient in a phase I study of BGB-283 in patients with B-RAF or K-RAS mutations. BGB-283 is an investigational, oral, selective, potent second generation inhibitor of B-RAF, making it a targeted therapeutic candidate to potentially treat and bring benefit to patients with cancers that harbour BRAF mutations and/or aberrations in the RAS-MAPK (mitogen-activated protein kinase) pathway.
“As the first second generation BRAF inhibitor to enter the clinic, BGB-283 represents one of the more exciting prospects in targeted cancer therapies,” said John Oyler, CEO of BeiGene. “BeiGene is dedicated to discovering and developing better targeted cancer therapeutics to address the unmet medical needs of cancer patients. We strive to use our deep understanding of cancer biology and translational medicine platform and our experience in drug discovery and development to bring more compounds like BGB-283 into the clinic.”
"We are very excited to have commenced dosing on the first-in-human trial of BGB-283, which has been specifically developed for the treatment of patients with BRAF and RAS driven cancers," said Dr Jayesh Desai, lead investigator at the Royal Melbourne Hospital and chair of the Cancer Trials Australia Phase I Group. "All patients enrolled onto this trial will be pre-selected based on having the appropriate genomic background. This approach will hopefully accelerate our ability to understand the safety, tolerability and efficacy of BGB-283."
BGB-283 is part of BeiGene’s two-asset strategic collaboration with Merck. Established earlier this year, the goal of the partnership is to leverage Merck’s global oncology development and commercialization expertise.
The phase I multi-centre, open-label, dose escalation clinical trial of BGB-283 is designed to assess the safety, tolerability and pharmacokinetic properties of BGB-283 as a single agent. The study is expected to only enroll subjects who have B-RAF or K-RAS mutations. Key objectives in the study include determining maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of BGB-283. Disease-specific expansion cohorts will be enrolled at the maximally tolerated or biologically relevant dose.
The mitogen-activated protein kinase (MAPK) pathway comprises several key signalling components that play critical roles in tumourigenesis. Alteration of the RAS-MAPK pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations mainly in the RAS or RAF genes. Activating mutations of the RAS family genes (H-RAS, K-RAS, and N-RAS) comprise up to 30 per cent of all human cancers. B-RAF mutations also have been reported in seven to eight per cent of all human cancers. Accordingly, components of this pathway are important therapeutic targets for cancer treatment.
BeiGene is an innovative Chinese oncology R&D company focusing on discovering, developing and commercializing targeted and immune-oncology therapeutics.