BerGenBio AS, an oncology biopharmaceutical company, announced that its multi-centre open label phase 1b trial (BGBC004) of BGB324, a selective inhibitor of Axl, in patients with stage IIIb and stage IV non-small cell lung cancer (NSCLC) in erlotinib-sensitive and refractory patients who have an activating EGFR mutation, is now underway at the University of Texas MD Anderson Cancer Center, Houston, Oncology Partners, Houston and at UT Southwestern Medical Center, Dallas, Texas, USA.

This multi-centre trial, which will enrol 66 patients, is designed to determine the maximum dose of BGB324 that can be safely administered in combination with erlotinib; identify the recommended phase 2 dose of BGB324; and evaluate the safety, pharmacokinetics and clinical activity of BGB324 in combination with erlotinib.

Professor John V Heymach, MD, PhD, professor and chair, Thoracic/head & Neck Medical Oncology at University of Texas MD Anderson Cancer Center said “Acquired resistance to erlotinib curtails the clinical utility of this drug in the treatment of NSCLC. BGB324’s novel mechanism holds tremendous potential for improving the treatment outcomes in this setting and I am excited to be able to offer my patients the drug in this clinical trial and look forward to reporting the outcomes in due course.”

 

Richard Godfrey, chief executive officer of BerGenBio, commented “The initiation of the NSCLC trial demonstrates our continuing clinical progress with BGB324, our first-in-class selective Axl inhibitor. This is our second phase 1b trial following the initiation of the acute myeloid leukaemia trial in November 2014 and we look forward to reporting results from these studies later in 2015.”

BGBC004 is a multi-centre, three arm, phase 1b trial which will enrol 66 patients with stage IIIb and stage IV non-small cell lung cancer (NSCLC). The first arm is designed to determine the maximum dose of BGB324 that can be safely administered in combination with erlotinib administered at the approved oral dose level of 150 mg daily and aims to identify the recommended phase 2 dose of BGB324. The second arm has a two-stage design to evaluate the safety, pharmacokinetics and clinical activity of BGB324 in combination with erlotinib in patients with an activating EGFR mutation who have progressed after receiving prior erlotinib. The third arm will evaluate the safety, pharmacodynamics and clinical activity of BGB324 when administered in combination with erlotinib in patients with an activating EGFR mutation who have received at least twelve weeks of erlotinib without disease progression.

BGB324 is a first-in-class, highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition (EMT), which is a key driver in drug-resistance and metastasis.

Non-small cell lung cancer (NSCLC) is an aggressive form of cancer, classified as any type of epithelial lung cancer other than small cell lung carcinoma. About 85 per cent to 90 per cent of lung cancers are NSCLC. There are three primary types of NSCLC: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. BerGenBio and others have shown that a primary mechanism of drug resistance in NSCLC is mediated by Axl and this resistance can be blocked by inhibiting Axl with BGB324.