On November 21, 2017 ArQule, Inc. (Nasdaq: ARQL) reported dosing of the initial patients in a registrational trial with its FGFR inhibitor, derazantinib (ARQ 087) in FGFR2 fusion driven second-line intrahepatic Cholangiocarcinoma (iCCA) (Press release, ArQule, NOV 21, 2017, View Source [SID1234522186]). The trial is planned to enroll up to 100 iCCA patients and provides an opportunity for a conditional approval as part of a fast-to-market strategy. Derazantinib is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family.
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The open-label single-arm trial will be recruiting initially in the U.S. and subsequently in Europe with objective response rate (ORR) as the primary endpoint. Derazantinib will be dosed orally once a day at 300 mg. FGFR2 fusion status will be determined by a break apart FISH assay. An interim analysis will be performed after the first 40 patients have been enrolled and evaluated for response.
"iCCA is a rare and difficult disease to treat," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "The durable response rate of 21% we observed in the phase 1/2 iCCA FGFR2 fusion driven trial has lead us to design the first registrational trial with a biomarker for this patient population. We are happy to report that recruitment is off to a great start with four patients already dosed."
Patients with advanced iCCA who relapse after first-line multi-agent chemotherapy have limited treatment options with poor prognosis. In recent years, FGFR2 fusions have been recognized as a potential iCCA-specific therapeutic target. The company has been granted orphan drug designation by the U.S. Food and Drug Administration and European Medicines Agency for derazantinib in this indication.
About Intrahepatic Cholangiocarcinoma
Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC)1. Depending on the anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA), and extrahepatic (eCCA). iCCA originates from the intrahepatic biliary ductal system and forms an intrahepatic mass. The average age adjusted incidence rate for iCCA is approximately one in 100,000 per year in the United States and Europe2,3.
About FGFR and Derazantinib (ARQ 087)
Derazantinib is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor ("FGFR") family with demonstrated efficacy in FGFR2 genetic alterations. The FGFR pathway is disrupted in several ways in human cancer, thus providing numerous therapeutic targets for an inhibitor of this pathway. Derazantinib has demonstrated in vivo inhibition of tumor growth and downstream signaling in tumors whose growth is driven by FGFR.
Signals of single agent activity with this drug were observed in phase 1a testing. Phase 1b expansion cohorts with derazantinib include patients with cholangiocarcinoma and adrenocortical tumors, as well as those with FGFR translocations, amplifications and mutations. Clinical development of derazantinib advanced into phase 2 for intrahepatic cholangiocarcinoma (iCCA) in patients with FGFR2 fusions following the observation of two confirmed responses in this patient population in the phase 1 portion of the program and a registrational trial is being conducted in this same patient population.