On September 4, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that it has initiated FRESCO-2, a Phase III registration study of fruquintinib for the treatment of patients with metastatic colorectal cancer ("CRC") in the U.S., Europe and Japan (Press release, Hutchison China MediTech, SEP 4, 2020, https://www.chi-med.com/chi-med-initiates-fresco-2-a-global-phase-iii-trial-of-fruquintinib-in-metastatic-crc/ [SID1234564465]). The first patient was dosed on September 3, 2020, in the U.S.
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FRESCO-2 is a randomized, double-blind, placebo-controlled, multicenter trial being conducted in patients with metastatic CRC. The primary endpoint of the study is overall survival. This large phase III trial will be enrolled in approximately 130 sites in 10 countries. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539.
The U.S. Food and Drug Administration ("FDA") granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020. Clinical data including the completed Phase III FRESCO study in Chinese patients and this FRESCO-2 global study, if positive, would support a future New Drug Application (NDA) for the treatment of patients with advanced metastatic CRC (third-line and above), based on our agreement with the FDA. The FRESCO-2 study design was also reviewed and endorsed by the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).
About CRC
CRC is cancer that starts in either the colon or rectum. CRC is the third most common cancer worldwide, causing more than 860,000 deaths in 2018.[1] In the U.S., it is estimated that 150,000 people will be diagnosed with CRC and 53,000 people will die from CRC in 2020.[2] In Europe, CRC is the second most common cancer, with an estimated 490,000 new cases and 240,000 deaths in 2018.[3] In Japan, CRC is the most common cancer, with an estimated 150,000 new cases and 57,000 deaths in 2018.[4]
About Fruquintinib
Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptor ("VEGFR") 1/2/3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
Chi-Med retains all rights to fruquintinib outside of China and is partnered with Eli Lilly and Company ("Lilly") in China.
About Fruquintinib in metastatic CRC
Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched by Lilly in late November 2018 under the brand name Elunate. Elunate is for the treatment of patients with metastatic CRC that have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
In December 2017, Chi-Med initiated a multi-center, open-label, Phase I/Ib clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors (clinicaltrials.gov identifier: NCT03251378). Proof-of-concept cohorts in patients with metastatic CRC and metastatic breast cancer were added in 2019.
Other Fruquintinib Development
Gastric Cancer in China: In October 2017, Chi-Med initiated the FRUTIGA study, a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for second-line treatment of advanced gastric or esophagogastric junction ("GEJ") adenocarcinoma. The trial is designed to enroll patients who did not respond to first-line standard chemotherapy. Subjects will receive either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. Patients will be randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumor type and performance status. The primary efficacy endpoint is overall survival. Secondary efficacy endpoints include progression-free survival (as defined by RECIST 1.1), objective response rate, disease control rate, duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored (clinicaltrials.gov identifier NCT03223376). In June 2020, Chi-Med completed a planned interim data review. Based on the preset criteria, the Independent Data Monitoring Committee (IDMC) recommended that the trial continue.
Immunotherapy combinations: Chi-Med has entered into three collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with programmed death-1 (PD-1) monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd.), Tyvyt (sintilimab, IBI308, developed by Innovent Biologics, Inc.) and geptanolimab (GB226, developed by Genor Biopharma Co. Ltd.).