ASLAN Pharmaceuticals, a specialty pharmaceutical company, has reported positive results of a phase II clinical trial with ASLAN001, a small-molecule pan-HER inhibitor, in gastric cancer. ASLAN001 reduced cell proliferation and cell survival in gastric tumours that were either coexpressing EGFR and HER2 or that were HER2 amplified.
ASLAN001 was invented by Array BioPharma Inc and licensed to ASLAN in 2011.
“This is the first time a drug has shown activity in this patient population,” said Dr Alan Barge, ASLAN’s chief medical officer. “The burden of gastric cancer is particularly severe in Asia. It is the most prevalent cancer in males in China, where it is estimated to affect over half a million people.”
The phase II, open-label, multicentre study was conducted at Seoul National University Hospital, South Korea, and was designed to evaluate the biological activity of ASLAN001 in patients with recurrent/metastatic gastric carcinoma whose tumours were HER2 amplified or coexpressing EGFR and HER2. 23 patients, who had previously failed on one or more rounds of chemotherapy and, where eligible, trastuzumab, each received 500mg of ASLAN001 orally twice daily as monotherapy for 28 days. Tumour biopsies taken before and after treatment were analysed using immunohistochemistry.
In this heavily pretreated population, ASLAN001 led to a downregulation of signalling pathways responsible for cell proliferation, and a reduction in cell survival and cell proliferation. Toxicities observed were consistent with other drugs in this class and the previously reported profile of this compound.
ASLAN intends to begin a randomised phase IIb study in gastric cancer and is exploring the use of ASLAN001 in other indications.
ASLAN001 is a novel, selective and oral HER2 / EGFR inhibitor, and has previously shown clinical activity in both HER2 positive and EGFR positive tumours in studies run by Array in the US. Over 200 patients have received ASLAN001 either as monotherapy or in combination with chemotherapy.
Gastric cancer is a major public-health problem in Asia. Patients with locally advanced, metastatic and recurrent disease have a poor prognosis, with an overall median survival of approximately 11 months. EGFR and HER2 receptors are commonly overexpressed together in gastric cancer. Recent data from pivotal studies of trastuzumab (Herceptin) indicate that the activity of this drug is limited to the subset of patients whose disease has amplified copies of the HER2 gene. ASLAN001 has the potential to augment or supersede the activity of trastuzumab in this population, and in the broader population of gastric cancers that coexpress both EGFR and HER2 receptors.
ASLAN Pharmaceuticals develops novel medicines for global markets and focuses on oncology and inflammatory diseases that are more prevalent in Asia.