On June 5, 2016 Xcovery, a developer of targeted therapeutics for cancer, reported that results from an expansion cohort in the ongoing Phase I/II clinical study of its investigational tyrosine kinase inhibitor (TKI), ensartinib (X-396), in patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 held in Chicago, Illinois (Press release, Xcovery, JUN 5, 2016, View Source [SID:1234513092]).
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Results from this multicenter expansion study demonstrated that ensartinib is well-tolerated and induces response in both crizotinib-naive and crizotinib-resistant ALK-positive NSCLC patients, as well as patients with CNS disease. The results also showed that plasma NGS with the Resolution ctDxTM blood-based platform may be used to detect ALK kinase domain mutations to select patients for therapy and monitor changes in response to treatment in a non-invasive manner. Results were presented by Dr. Leora Horn, MD, MSc, Vanderbilt University Medical Center, in a poster titled "Plasma genotyping of patients in the eXalt2 trial: ensartinib+ (X-396) in ALK-positive non-small cell lung cancer (NSCLC)."
"Ensartinib has shown promising activity in ALK-positive NSCLC patients with durable responses observed in patients who are crizotinib-naïve and patients with resistance to crizotinib and second generation ALK tyrosine kinase inhibitors," said Dr. Horn. "The plasma sequencing of patients in the expansion study have identified a potential way to identify and select patients for therapy and to monitor for response and the development of acquired resistance."
About the Expansion Cohort of the Phase I/II "eXalt2" Study
In this multicenter study, 38 patients with ALK-positive (via FISH or IHC) advanced or recurrent NSCLC were treated with at least 200mg of ensartinib on 28-day cycles with plasma samples collected on the first day of each cycle. Major inclusion criteria for the expansion cohort included: ALK-positive (via FISH or IHC) advanced or recurrent NSCLC, measurable disease and ECOG performance status (PS) 0-1. Asymptomatic treated or untreated brain metastases (CNS) and leptomeningeal disease were allowed.
Key conclusions from the study include:
Ensartinib has shown promising activity in ALK-positive NSCLC patients with durable responses observed in patients who are crizotinib-naïve and patients with resistance to crizotinib and second generation ALK TKIs.
Plasma NGS can be used to detect ALK kinase domain mutations and monitor changes in response to treatment in a non-invasive manner.
In this study, ALK kinase domain mutations were detected in 4/11 patients who had prior crizotinib and 2/4 patients who had prior crizotinib and ceritinib. G1202R was found in both of the latter cases.
1/2 patients whose plasma detected the G1202R mutation prior to start of the trial responded to ensartinib.
Further study of this methodology is ongoing to correlate the presence of ALK kinase domain mutations with response and resistance to ALK TKI therapy.
A Phase III trial is ongoing comparing ensartinib to crizotinib in TKI naïve ALK-positive NSCLC patients.
About Ensartinib (X-396)
Xcovery’s lead asset is X-396, a small molecule, anaplastic lymphoma kinase (ALK) inhibitor. It is being studied in the Xalt2 Study, a phase II trial for the treatment of ALK-positive non-small cell lung cancer (NSCLC). The Xalt2 Study is currently enrolling patients. To learn more, visit: www.xalt2study.com or ClinicalTrials.gov under trial identifier NCT01625234.
About NSCLC and ALK
Lung cancer is the second most common type of cancer identified in the United States with an estimated 221,000 new diagnoses expected in 2015. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for an estimated 85-90% of the lung cancer cases. The anaplastic lymphoma kinase (ALK) gene is located on chromosome 2 and rearrangement of the ALK gene can lead to its activation or expression, therefore increasing a person’s chance of developing certain types of cancer, including NSCLC. Between three and seven percent of patients with NSCLC have the ALK rearrangement, making this a molecular target warranting investigation for NSCLC patients.