Aslan Pharma’s Phase II Gastric Cancer Drug Fails to Hit Endpoints

ASLAN Pharmaceuticals’ first-line therapy for HER1/HER2 co-expressing cancer tumors failed to meet primary endpoints in a mid-stage trial after 12 weeks of treatment, the company announced Sunday.

Singapore-based Aslan, reported that Varlitinib (ASLAN001), a highly potent, oral, reversible, small molecule pan-HER inhibitor, combined with mFOLFOX6 shrunk tumors by an average of 22 percent compared to 12.5 percent shrinkage by mFOLFOX6 alone. That difference did not reach statistical significance, the company said. The company was testing the combination medicine as a potential treatment in advanced or metastatic gastric cancer patients who have HER1/HER2 co-expressing tumors. Varlitinib was designed to target the human epidermal growth factor receptors HER1, HER2 and HER4.

Aslan did report that following a review of 17 progression-free survival (PFS) events to date, there was a “trend towards an improvement in PFS in patients treated with varlitinib.” There were no significant tolerability concerns reported by the company. Aslan said that 73.1 percent of patients taking varlitinib experienced a grade 3 or higher adverse event compared to 88.5 percent of patients taking mFOLFOX6 alone.

Aslan said that the proportions of patients who showed the best performance status, an ECOG status of 0, was much higher in the placebo arm than in the varlitinib arm. The report was 46.2 percent for control and 19.2 percent for varlitinib, the company said.

Mark McHale, Aslan’s chief operating officer, noted that first-line gastric cancer treatment is a “very challenging indication to treat.” The majority of patients in this setting present with an advanced form of the disease at initial diagnosis. As of this time, McHale said that there have been no targeted therapies approved to treat gastric cancer with low HER-family expression.

“Whilst we are disappointed by the study findings, we are encouraged by the positive safety data and remain confident that varlitinib’s potent pan-HER inhibition has the potential to yield benefits in biliary tract cancer where HER family expression is known to be high,” McHale said in a statement.

While the trial fell short of statistical significance, McHale said the company will analyze the data from the study and plan to publish the reports at a future date. Additionally, the company said it will focus on the development of varlitinib in biliary tract cancer and other indications where the medicine has shown activity. McHale said the company will present upcoming data in first-line biliary tract cancer at ASCO GI in San Francisco later this week. Aslan also anticipates topline data from its study in second-line biliary tract cancer in the second half of 2019.

In the United States, varlitinib has been granted orphan drug designation for gastric cancer and cholangiocarcinoma, a sub-type of biliary tract cancer.

Earlier this month, Aslan announced the U.S. Food and Drug Administration (FDA) concluded a 30-day review of an Investigational New Drug Application for another asset, Aslan003, an inhibitor of human dihydroorotate dehydrogenase, for a Phase II trial for acute myeloid leukemia. Aslan plans to begin the clinical trial in the first half of this year.