CH5424802 was identified as a potent, selective, and oral anaplastic lymphoma kinase (ALK) inhibitor with a unique chemical scaffold. The first in human phase I/II study targeting patients with ALK-positive non-small-cell lung cancer (NSCLC) is ongoing. Here we report the outcomes of the phase I portion.Methods
Patients were administered a single dose of CH5424802 under fasting conditions, followed 72 h later by twice daily dosing for 21 days. They were then evaluated for dose limiting toxicity (DLT). Administration was continued until disease progression.Results
A total of 15 patients (M/F: 9/6) were treated with CH5424802 under fasting conditions in six cohorts (20 mg bid to 300 mg bid). Median age was 42 years. A DLT was not determined. Thus, the highest dose level defined in the protocol (300 mg bid) did not reach the maximum tolerated dose (MTD). Frequent toxic effects (no. of cases) were constipation (6), neutropenia (5), and myalgia (5). Grade 3 toxic effects were hypophosphatemia (2), neutropenia (2), blood CPK increased (1), and hypermagnesemia (1). Nausea was mild (2 cases of grade 1), and for eye disorders, which are thought to be characteristic of crizotinib, only 2 grade 1 cases were observed. PK data showed T1/2 ranging from 16 to 42 h, and dose-dependent increases of Cmax and AUC. All patients at all dose levels achieved tumor regression. At dose levels of 240 mg bid or more, all 7 patients with measurable lesions achieved a partial response. So far, 11 patients have been on study treatment >6 months.Conclusion
CH5424802 was well tolerated with promising efficacy in patients with ALK-positive NSCLC. The phase II portion is ongoing.