On October 27, 2015 ArQule, Inc. (Nasdaq:ARQL) reported that six posters, with pre-clinical and clinical data for tivantinib, ARQ 087, ARQ 092, and ARQ 751, will be presented at the AACR (Free AACR Whitepaper)-NCI-EORTC Conference in Boston, Mass (Press release, ArQule, OCT 27, 2015, View Source [SID:1234507802]). All posters will be presented on November 7th from 12:30 p.m. to 3:30 p.m. as part of Poster Session B in Exhibit Hall C-D.
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Poster Presentations
Poster Number: B111
Poster Title: Efficacy of AKT Inhibitor ARQ 092 Compared with Sorafenib in a Cirrhotic Rat Model with Hepatocellular Carcinoma
Poster Number: B151
Poster Title: In FGFR2 Driven Tumors, Preclinical Pharmacokinetics (PK), Pharmacodynamics (PD), and Efficacy Translate into Clinical Activity of ARQ 087
Poster Number: B181
Poster Title: Association of AKT1E17K and PIK3CAH1047R Mutations with Efficacy of ARQ 092 In Vitro, In Vivo and in Patients
Poster Number: B183
Poster Title: Targeting PI3K Pathway Dependent Endometrial Tumors with Allosteric Inhibitors, ARQ 092 and ARQ 751
Poster Number: B185
Poster Title: ARQ 092 Enhances the Efficacy of Paclitaxel, Lapatinib, Trastuzumab, Trametinib, and ARQ 087 both in Cancer Cell Lines and Mouse Xenograft Cancer Models
Poster Number: B194
Poster Title: Tivantinib in Combination with Erlotinib vs Erlotinib Alone for EGFR Mutant NSCLC: Subgroup Results from the Phase 3 MARQUEE Study
Precision Medicine
Tivantinib is enrolling in two biomarker-driven phase 3 trials, METIV-HCC and JET-HCC. ARQ 087 is enrolling in a biomarker-driven phase 2 trial in intrahepatic cholangiocarcinoma (iCCA) with FGFR translocations. ARQ 092 is enrolling in a phase 1b biomarker-driven trial in patients with AKT and PI3K activating mutations including patients with breast, endometrial and ovarian cancers.
About MET and tivantinib (ARQ 197)
Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in Phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.
Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in a number of tumors. Tivantinib has not yet been approved for any indication in any country.
In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.
About the AKT Pathway, ARQ 092 and ARQ 751
ARQ 092 and ARQ 751 are orally available, selective small molecule inhibitors of the AKT kinase. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.
ARQ 092, the lead compound in ArQule’s AKT program, has completed Phase 1a clinical testing and has advanced into Phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphoma and tumors harboring either AKT or PI3K mutations. A number of next-generation compounds in the Company’s AKT program are in early to late stages of pre-clinical development. The company plans to file an Investigational New Drug (IND) application by the end of 2015 for ARQ 751, a next generation AKT inhibitor.
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 amplified tumors. 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 inhibition of tumor growth and downstream signaling in vivo in tumors whose growth is driven by these targets.
Signals of single agent activity with this compound 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, amplification and mutations. Clinical development of ARQ 087 has advanced into Phase 2 for intrahepatic cholangiocarcinoma ("iCCA") following the observation of two confirmed partial responses in this patient population in the Phase 1 portion of the program.