Clinical Trials

Date: 2017-06-05

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: Hutchison China MediTech Limited "ChiMed" (China)

Product: fruquintinib

Action mechanism:

• tyrosine kinase inhibitor/VEGFR inhibitor. Fruquintinib (HMPL-013) is an orally available, small molecule inhibitor of vascular endothelial growth factor receptors (VEGFRs), with potential anti-angiogenic and antineoplastic activities. Upon oral administration, fruquintinib inhibits VEGF-induced phosphorylation of VEGFRs 1, 2, and 3 which may result in the inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and tumor cell death.  It is currently under the joint development in China by Chi-Med and its partner Eli Lilly. Chi-Med receives reimbursement for costs associated with clinical development in China from Lilly according to a pre-specified cost-sharing rate.
• Two late-stage, pivotal Phase III registration studies are ongoing in colorectal cancer (FRESCO) and lung cancer (FALUCA). In addition, fruquintinib is also in clinical development for gastric cancer. A new drug application (NDA) for fruquintinib to the China Food and Drug Administration (CFDA) is expected to be filed in mid-2017.

 

Disease: locally advanced or metastatic colorectal cancer

Therapeutic area: Cancer - Oncology

Country: China

Trial details:

• FRESCO is a randomized, double-blind, placebo-controlled, multicenter, Phase III pivotal trial in patients with locally advanced or metastatic colorectal cancer who have failed at least two prior systemic antineoplastic therapies  (third-line), including fluoropyrimidine, oxaliplatin and irinotecan. The first patient was dosed on December 12, 2014. A total of 416 patients were randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC; or placebo plus best supportive care. The primary endpoint is OS, with secondary endpoints including PFS, objective response rate, disease control rate and duration of response. Once a pre-specified number of OS events (deaths) have occurred, data analysis will commence  The trial was concluded on January 17, 2017.
• The FRESCO trial was launched following a 71-patient, randomized, double-blind Phase II trial of fruquintinib as a third-line treatment for metastaticolorectal cancer.
• (NCT02314819)

Latest news:

• • On June 5, 2017, Chi-Med announced that results from its pivotal Phase III trial with fruquintinib, its novel vascular endothelial growth factor receptor (VEGFR”) kinase inhibitor, were highlighted in an oral presentation  during the American Society of Clinical Oncology Annual Meeting.  Results showed that the FRESCO trial, a randomized, double-blind, placebo-controlled, multi-centered Phase III trial assessing fruquintinib in patients with locally advanced or metastatic colorectal cancer in China, met all primary and secondary endpoints including significant improvements in overall and progression-free survival.
•  Efficacy Results: The primary endpoint of median overall survival (OS) was 9.30 months [95% CI 8.18–10.45] in the fruquintinib group vs. 6.57 months [95% CI 5.88–8.11] in the placebo group, with a hazard ratio of 0.65 [95% CI: 0.51–0.83; two-sided p<0.001].  
•  The secondary endpoint of median progression-free survival (PFS) was 3.71 months [95% CI 3.65–4.63] in the fruquintinib group vs. 1.84 months [95% CI 1.81–1.84] in the placebo group, with a hazard ratio of 0.26 [95% CI: 0.21–0.34; two-sided p<0.001].
•  Significant benefits were also seen in other secondary endpoints.  The fruquintinib group disease control rate was 62.2% vs. 12.3% for placebo (p<0.001), while the overall response rate was 4.7% vs. 0% for placebo (p=0.012).
• Safety and Tolerability Results: Results showed that fruquintinib had a manageable safety profile with lower off-target toxicities compared to other targeted therapies, and did not demonstrate the sometimes severe and fatal hepatotoxicity (liver toxicity) observed with other therapies in this disease setting.
• The most frequently reported fruquintinib-related grade ?3 adverse events included hypertension (21.2%), hand-foot skin reaction (10.8%), proteinuria (3.2%) and diarrhea (2.9%), all associated with VEGFR inhibition.  No other grade ?3 adverse events exceeded 1.4% in the fruquintinib population, including hepatic function adverse events such as elevations in bilirubin (1.4%), alanine aminotransferase (ALT) (0.7%) or aspartate aminotransferase (AST) (0.4%).  
•  Dose interruptions or reductions occurred in only 35.3% and 24.1% of patients in the fruquintinib arm, respectively, and only 15.1% of patients discontinued treatment vs. 5.8% for placebo.
•  Chi-Med expects to complete the New Drug Application (NDA) submission for fruquintinib to the China Food and Drug Administration imminently.  The Company also expects to initiate U.S. clinical studies in 2017.
•  • On May 13, 2016, Chi-Med announced that it has completed patient enrollment of FRESCO, its Phase III pivotal trial of fruquintinib (HMPL-013) in third-line locally advanced or metastatic colorectal cancer  in China.

Is general: Yes