On June 3, 2017 ArQule, Inc. (Nasdaq: ARQL) reported that data from a phase 1/2 trial with fibroblast growth factor receptor (FGFR) inhibitor, ARQ 087, presented at ASCO (Free ASCO Whitepaper) demonstrate a meaningful clinical benefit to intrahepatic cholangiocarcinoma (iCCA) patients harboring FGFR2 fusions (Press release, ArQule, JUN 3, 2017, View Source [SID1234519376]). The data show a robust response rate and prolonged duration of therapy for these patients well in excess of that reported for second-line chemotherapy. These data support future development of ARQ 087 as second-line treatment, and a registrational phase 3 trial in iCCA FGFR2 fusion positive patients is planned to begin in the third quarter of 2017. ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family.
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The presentation titled "ARQ 087, an oral pan-Fibroblast Growth Factor Receptor (FGFR) inhibitor, in patients with advanced intrahepatic cholangiocarcinoma (iCCA) with FGFR2 genetic aberrations" can be viewed at View Source
ARQ 087 Results from Phase 1/2 iCCA Trial Presented at ASCO (Free ASCO Whitepaper)
The data is comprised of 35 iCCA patients harboring FGFR2 genetic alterations, of which 29 patients were FGFR2 fusion positive. All 29 of these patients were evaluable for this data presentation.
The objective response rate for iCCA FGFR2 fusion positive patients was 21% (six partial responses) and the disease control rate was 83% (six partial responses and 18 patients with stable disease). Patients were evaluated using Standard RECIST (Response Evaluation Criteria in Solid Tumors).
Clinical benefit was observed in 72% of FGFR2 fusion positive patients defined as partial response (six patients) and stable disease (15 patients) for at least 16 weeks.
The median duration of therapy observed in iCCA FGFR2 fusion positive patients was 182 days. In these same patients, the median duration of front-line chemotherapy was 119 days.
ARQ 087 showed a manageable safety profile with mostly Grade 1 and 2 adverse events.
Nine patients with FGFR2 fusions are on-going in the trial.
"Clinical evidence is accumulating on the role of FGFR inhibitors in cholangiocarcinoma and other FGFR driven tumors such as urothelial and gastric cancers," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "We are encouraged to see that both the response rate and disease control rate were consistent throughout the trial. Patients with iCCA often have a poor prognosis for front-line treatment with chemotherapy, and there are no currently approved second-line therapeutic options."
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 ARQ 087 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 ARQ 087
ARQ 087 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. ARQ 087 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 ARQ 087 include patients with cholangiocarcinoma and adrenocortical tumors, as well as those with FGFR translocations, amplifications and mutations. Clinical development of ARQ 087 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 phase 3 registrational trial is planned to begin in the third quarter of 2017 in this same patient population.