Phase I study of safety and pharmacokinetics for CT-707 in ALK-positive advanced non-small cell lung cancer

Abstract

Background: CT-707 is an anaplasticlymphoma kinase(ALK)/focal adhesion kinase (FAK)/proline-rich tyrosine kinase-2 (Pyk2) inhibitor. The purpose of the study is to determine the maximum tolerated dose(MTD)/dose-limiting toxicity (DLT), pharma-cokinetics and efficacy of CT-707 in patients with ALK-positive non-small cell lung cancer (NSCLC) (NCT). Methods: Patients with advanced NSCLC harboring ALK fusion gene were enrolled for this study, including those who developed disease progression after treatment. The estimated doses of CT-707 were 50mg, 100mg, 200 mg, 300 mg, 450 mg, 600mg and 800 mg orally once daily, respectively. Results: 23 patients have been enrolled in total so far. One patient withdrew from the study and 22 patients had finished the toleration study. The dose escalation has reached 600mg. In 20 evaluable patients, the objective response rate and partial response rate were both 40%. 40% of patients had stable disease, the disease control rate was 80%. The adverse events (AEs) were grade 1-2, including aspartate transaminase elevation (22%), alanine transaminaseel elevation (17%), diarrhea (35%) and nausea (26%). Only one patient had a Grade 3 adverse event whose creatinine increased and DLT was observed. No drug-related serious AE was observed. A patient who had disease progression after crizotinib treatment received 450 mg CT-707 achieving a tumor shrinkage of 20% for 3 months. Once daily oral administration, of CT-707 was quickly absorbed, with time of maximum plasma concentrations (Tmax) ranging from 1 to 3 hours. Exposures (Cmax and AUC) appeared tobe linear. Conclusions: CT-707 was well-tolerated and highly effective in ALK-positive advanced NSCLC, including in crizotinib-pretreated patients. Further studies of toxicity, phar-macokinetics and efficacy will be conducted.