Hutchison China MediTech Limited reported preliminary clinical activity, safety, and tolerability data of fruquintinib, an investigational selective inhibitor of vascular endothelial growth factor receptor given in combination with Iressa®.
These data were from an ongoing Phase II proof-of-concept trial conducted in patients with epidermal growth factor receptor (“EGFR”) mutation-positive (“EGFRm”) non-small cell lung cancer (“NSCLC”). Preliminary data from this Phase II proof-of-concept trial, the first study assessing combining fruquintinib with another tyrosine kinase inhibitor, demonstrated promising efficacy and an acceptable safety profile. The data were presented at the International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan, October 15 to 18, 2017.
“Having proven efficacy as a monotherapy in colorectal cancer, fruquintinib is now demonstrating its tolerability and efficacy in innovative combinations which are made possible because of its high kinase selectivity, negligible off-target toxicity, and clean drug-drug interaction profile,” said Mr. Christian Hogg, Chief Executive Officer of Chi-Med. “In January 2017, preliminary tolerability and efficacy of fruquintinib in combination with chemotherapy, Taxol® (paclitaxel), was reported in a Phase I/II trial in gastric cancer. Now, this early Iressa® combination data further validates our long-held research approach to create highly selective and optimized drug candidates.”
The study assessed fruquintinib (4 to 5mg, once daily 3-weeks-on/1-week-off) in combination with Iressa® (250mg, once daily) in China as a first-line treatment for patients with EGFRm advanced NSCLC. The most common treatment-emergent adverse events (“AEs”) in 26 patients were increased aspartate aminotransferase (“AST”) (54%), increased alanine aminotransferase (“ALT”) (46%), increased total bilirubin (DBiL) (39%), increased thyroid stimulating hormone (TSH) (39%), and rash (35%). The eight (31%) grade 3 AEs were increased ALT (19%), increased AST (4%), proteinuria (4%), and hypertension (4%). There were no serious AEs or those that lead to death.
Preliminary results in 17 efficacy evaluable patients showed an overall response rate (ORR) of 76% (13/17) and a disease control rate (DCR) of 100% (17/17). Four partial responses were not yet confirmed at the time of data cut-off.
Fruquintinib (HMPL-013) is a highly selective small molecule drug candidate that has been shown to inhibit VEGF receptors 24 hours a day via an oral dose, without known off-target toxicities. Its tolerability, along with its clean drug-drug interaction profile, enables rational combination with other cancer therapies such as in our ongoing clinical trials of fruquintinib in combination with chemotherapy and targeted therapy. VEGF and VEGF receptors play a pivotal role in tumor-related angiogenesis.
Fruquintinib is currently under joint development in China by Chi-Med and its partner Eli Lilly and Company (“Lilly”). Chi-Med and Lilly jointly announced top-line results from the FRESCO colorectal cancer trial on March 3, 2017. In addition, fruquintinib is being studied in China in a Phase III pivotal trial in NSCLC, known as FALUCA; and a Phase II study using fruquintinib combined with Iressa® in the first-line setting for patients with advanced or metastatic NSCLC. Other studies currently being planned, and soon to be initiated, include a Phase III study in gastric cancer in combination with paclitaxel in China, new studies in the United States, and certain exploratory studies in combination with other oncology agents.
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
1 Lu S, et al. A Phase II Study of Fruquintinib in Combination with Gefitinib in Stage IIIb/IV NSCLC Patients Harboring EGFR Activating Mutations. Abstract #10907. Presented at the World Lung Cancer Congress 2017, Yokohama, Japan, 15-18 October 2017.