The drug failed to meet the primary endpoints of progression-free survival and overall response rate.
Singapore-based ASLAN Pharmaceuticals announced topline data from its TreeTopp (TREatmEnT OPPortunity with varlitinib in biliary tract cancer) trial in second-line biliary tract cancer (BTC). The drug failed to meet the primary endpoints of progression-free survival (PFS) and overall response rate (ORR).
Varlitinib is an oral, reversible, small molecule pan-HER inhibitor that targets the human epidermal growth factor receptors, HER1, HER2 and HER4. These receptors are mutated or overexpressed in numerous cancer types, resulting in excessive proliferation and uncontrolled growth. The drug has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for gastric cancer and cholangiocarcinoma, a sub-type of biliary tract cancer. It also received orphan drug designation for biliary tract cancer by South Korea’s Ministry of Food and Drug Safety.
The trial was a global, double-blind, randomized two-arm study that enrolled 127 patients who failed first-line therapy. There were 56 sites in the U.S., Europe, Japan, Australia and other parts of Asia.
In the trial, the median PFS was 2.83 months for varlitinib in combination with capecitabine compared to a median PFS of 2.79 in the control arm. In the varlitinib arm, ORR was 9.3% compared to 4.8% in the control arm.
The trial didn’t hit statistical significance, but Aslan notes that a pre-planned exploratory analysis identified a sub-group with improved efficacy. That analysis was also supported by retrospective review of the JADETREE trial in China, which evaluated the drug in combination with capecitabine in second-line BTC patients.
“The results from the study are disappointing,” said Carl Firth, Aslan’s chief executive officer. “They will, however, provide the scientific community with important insights into an aggressive and under-researched disease that presents a growing burden of care worldwide as prevalence arises.”
Firth added, “I would like to extend our thanks to the patients, trial investigators and site personnel who participated in the study and to the Aslan team for their commitment to the development of varlitinib. Aslan remains focused on the promising molecules in its portfolio, including the ongoing study in atopic dermatitis of ASLAN004, our IL-13 receptor antibody which blocks signaling through IL-4 and IL-13. We look forward to the interim readout in early 2020.”
Biliary tract cancer is a rare cancer of the bile tract, which is the tubes that transport bile produced by the liver into the small intestines. Two bile ducts originate from the liver and one from the gallbladder. They connect to form the common bile duct that connects to the small intestine. When food is digested, bile stored in the gall bladder is released and moves through the bile ducts into the small intestine.
Biliary tract cancer can develop anywhere along the bile ducts. Another name for bile duct cancer is cholangiosarcoma. Additional names depend on where on the bile ducts the cancer is diagnosed. It is generally very difficult to treat.
The company reported its third-quarter financials on October 29. In addition to the financial information, the company noted that it had presented late-breaking topline data from its Phase II trial in China of varlitinib and capecitabine in second-line BTC at the Chinese Society of Clinical Oncology meeting. In that trials, patients showed a response rate of 11%, including two complete responses, and median progression free survival was 2.7 months and OS was 5.8 months, which was still maturing. They pointed out that patients in the study seemed to present with a more aggressive disease with only 10% of patients responding to first-line gemcitabine-based treatment before enrollment.
The company also presented new data from a Phase Ib open-label, dose escalation trial of varlitinib in combination with modified irinotecan and infusional 5-fluorouracil chemotherapy at the 2019 European Society for Medical Oncology Congress. The OS was 13% and the median PFS was 4.2 months.
