Date: 2016-01-28
Type of information: update on patient enrollment
phase: 1
Announcement: update
Company: ArQule (USA - MA)
Product: ARQ 092
Action
mechanism: AKT inhibitor/kinase inhibitor. ARQ 092 is an orally bioavailable inhibitor of the serine/threonine protein kinase AKT (protein kinase B) with potential antineoplastic activity. AKT inhibitor ARQ 092 binds to and inhibits the activity of AKT in a non-ATP competitive manner, which may result in the inhibition of the PI3K/AKT signaling pathway. This may lead to the reduction in tumor cell proliferation and the induction of tumor cell apoptosis. Pre-clinical study tested the efficacy of ARQ 092 in suppressing AKT signaling in cells and tissues from patients with Proteus syndrome. Reduced phosphorylation of AKT and downstream targets of AKT in a concentration-dependent manner were observed in as little as two hours without reduction in cell viability.
Disease: Proteus syndrome
Therapeutic area: Rare diseases - Genetic diseases
Country: USA
Trial
details: Proteus syndrome is a rare segmental overgrowth disorder caused by a somatic gain of function mutation in the oncogene AKT1, encoding the AKT1 kinase. The disorder is progressive, with high morbidity and mortality there are very few living adults with this disease. This mutation causes constitutive activation of AKT1, through Ser473 and Thr308 phosphorylation. This activation stimulates the AKT/PI3K pathway, mediating processes including increased cell proliferation and decreased apoptosis. ArQule has developed a small molecule, ARQ 092 that effectively inhibits AKT, with the lowest IC(50) for AKT1 (as compared to AKT2 or AKT3, and orders of magnitude lower for other kinases). (NCT02594215)
Latest
news: * On January 28, 2016, ArQule announced a pipeline update for its AKT inhibitors, including ARQ 092 and ARQ 751, both orally available, selective pan-AKT inhibitors. The phase 1 trial for ARQ 092 in Proteus syndrome, which was opened for enrollment in November 2015 , has completed dosing of its first cohort. The first cohort, consisting of three patients, is being observed for safety. The phase 1 trial is being conducted by our collaborators at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH).
ArQule continues to enroll patients harboring AKT1 or PI3K mutations in the company sponsored phase 1b expansion cohort of its oncology trial. Cohorts for lymphoma and endometrial are fully enrolled. Thus far the company has observed five partial responses in the phase 1b portion of the trial, three of which occurred in patients whose tumors have AKT1 or PI3K mutations and two of which occurred in patients where the mutational status is unknown.
