Anti-ALK (mutation R1275Q) Monoclonal Antibody, clone XH007

Objective. The aim of this study was to unveil the reciprocal relation of tumor characteristics and inflammation in inflammatory myofibroblastic tumor in the head and neck. Study Design. The study included a retrospective cohort of patients with inflammatory myofibroblastic tumors treated between 2005 and 2017 in a tertiary hospital. Tumor features and inflammation were assessed through the expression of anaplastic lymphoma kinase (ALK), the degree of inflammation and cyclooxygenase-2 (COX-2) expression. The prognostic factors were analyzed for overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. Results. Forty-one patients diagnosed with inflammatory myofibroblastic tumors were followed up, and 41 paraffin sections were obtained. The positive rate of ALK expression was 21 (51.2%) of 41 patients. Nineteen patients had high-grade ALK expression, and 22 patients had low-grade ALK expression. Thirty-nine patients had high-grade inflammation, and 2 had low-grade inflammation. The positive rate of COX-2 expression was 100%. Tumors with both high-grade ALK expression and inflammation had worse DFS (P =.015). The multivariate Cox analysis showed that the grades of ALK expression and inflammation (P =.004) were independent risk factors for DFS. Conclusions. Because of the latent synergistic effects of ALK and inflammation in the tumorigenesis of inflammatory myofibroblastic tumor, the combined therapy of ALK and COX-2 inhibitors shows promise.

Purpose Ensartinib is a novel, potent and highly selective inhibitor of anaplastic lymphoma kinase (ALK) that has promising clinical activity and low toxicity in patients with ALK-positive non-small cell lung cancer. This study was conducted to investigate the pharmacokinetics, metabolism and excretion of ensartinib following a single 200 mg/100 mu Ci oral dose of radiolabeled ensartinib to healthy subjects. Methods Six healthy male subjects were enrolled and administrated an oral suspension in a fasted state. Blood, urine and feces were collected. Radioactivity concentrations were measured by liquid scintillation counting and plasma concentrations of ensartinib by liquid chromatography-tandem mass spectrometry. Both techniques were applied for metabolite profiling and characterization. Results The mean total recovery was 101.21% of the radiolabeled dose with 91.00% and 10.21% excreted in feces and urine, respectively. Unchanged ensartinib was the predominant drug-related component in urine and feces, representing 4.39% and 38.12% of the administered dose, respectively. Unchanged ensartinib and its metabolite M465 were the major circulating components, accounting for the same 27.45% of the plasma total radioactivity (AUC(0-24h)pool), while other circulating metabolites were minor, accounting for less than 10%. MeanC(max), AUC(0-infinity,)T(1/2)andT(max)values for ensartinib in plasma were 185 ng/mL, 3827 h ng/mL, 18.3 h and 3.25 h, respectively. The total radioactivity in plasma was cleared with terminal half-life of 27.2 h. Treatment with ensartinib was well tolerated, and no serious adverse events were reported. Conclusion It was well tolerated in the six healthy male subjects following a single oral administration of 200 mg/100 mu Ci dose of ensartinib. Besides unchanged ensartinib, metabolite of M465 was the predominant circulating drug-related component. The drug was primarily eliminated in feces.