–Activity shown in both crizotinib-naïve and crizotinib-resistant ALK+ NSCLC patients– -X-396 is well-tolerated with limited toxicities-
WEST PALM BEACH, Fla.–(BUSINESS WIRE)–June 3, 2014–
Xcovery, a developer of next-generation targeted therapeutics for cancer, today presented preliminary results at the annual meeting of the American Society for Clinical Oncology (ASCO) from a phase 1 study of X-396, a potent small molecule anaplastic lymphoma kinase (ALK) inhibitor, that showed X-396 is well tolerated and has antitumor activity in patients with ALK positive non-small cell lung cancer (NSCLC).
“Responses to X-396 have been observed in both patients that are crizotinib naïve and those that have developed resistance to treatment with crizotinib,” said Leora Horn, M.D., M.Sc., Associate Professor of Medicine and Clinical Director, Thoracic Oncology Program at Vanderbilt-Ingram Cancer Center, Nashville, and lead-investigator on the phase 1 study. “Responses also have been observed in patients with brain metastases. The clinical safety profile for X-396 is favorable and different from other ALK inhibitors.”
Xcovery is developing X-396 for the treatment of solid tumors where ALK is deregulated. X-396 has been validated in potency and selectivity assays indicating that it is more selective and up to 10 times more potent than competitive ALK inhibitors. X-396 has been active in animal models of NSCLC and neuroblastoma. Importantly, X-396 has shown activity in ALK mutations that confer resistance to other small molecule ALK inhibitors.
“We believe the results from our phase 1 study presented at ASCO further validate the clinical potential of X-396 as an effective, well tolerated oral treatment for ALK positive NSCLC, lymphoma, and neuroblastoma,” said Dr. Chris Liang, executive vice president and chief scientific officer at the Xcovery Group of companies.
Preliminary Phase 1 Results of X-396 in ALK+ NSCLC
Title: A phase I trial of X-396, a novel ALK inhibitor, in patients with advanced solid tumors.
Presenter: Leora Horn, M.D., M.Sc., Vanderbilt-Ingram Cancer Center
Poster Presentation: Tuesday June 3, 8:00 a.m. – 11:00 a.m. (CT) Room E354b
Abstract Number: 8030
Interim results were presented from a dose-escalation phase 1 study evaluating X-396 in patients with advanced solid tumors. Primary study objectives included determining recommended dose of X-396 as a single agent and safety and tolerability of the compound for clinical evaluation going forward. Patients received X-396 daily in 28 day cycles with escalating doses starting at 25 mg daily. At the time of data cutoff, 35 patients were enrolled. Tumor types included NSCLC, head & neck, small cell lung, colorectal, and breast cancers. The NSCLC (n=27) patient group was comprised of ALK-positive patients (n=18) who were either crizotinib-naïve (n=5) or crizotinib-resistant (n=13). Among 11 ALK positive patients evaluable for response (patient completed one cycle and had post baseline response assessment) -6 patients had a partial response (55%) and 2 had stable disease (18%). For the three patients with progressive disease, two were at lower doses (50 mg, 100 mg) with acquired resistance to crizotinib and one (at 250 mg) was resistant to both crizotinib and ceritinib. This crizotinib and ceritinib resistant patient had a complete response in retroperitoneal lymph node but progression of bone and CNS metastases.
Common adverse events included low-grade (Grade 1 or 2) nausea, rash, vomiting, fatigue, and edema. Two dose-limiting toxicities (DLTs) were observed: fluid overload (200 mg) and rash (250 mg). X-396 is generally well tolerated at doses up to 250 mg daily. The maximum tolerated dose (MTD) has not been officially reached.
Xcovery is a clinical-stage company focused on the development of next-generation targeted therapeutics for cancer. Founded by Sheridan G. Snyder and Chris Liang, Ph.D., Xcovery’s vision is to successfully develop innovative oncology therapies to optimize patient outcomes. Through innovative drug design, Xcovery has developed a comprehensive pipeline of oncology therapies that target a wide range of advanced tumors. For more information, please visit www.xcovery.com.
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