a phase ii, single-arm, open-label, multicenter study to evaluate the efficacy and safety of p276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma论文.pdfVIP

Original Study A Phase II, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of P276-00, a Cyclin-Dependent Kinase Inhibitor, in Patients With Relapsed or Refractory Mantle Cell Lymphoma Ryan D. Cassaday,1 Andre Goy,2 Suresh Advani,3 Purvi Chawla,4 Rajesh Nachankar,4 Mansi Gandhi,4 Ajay K. Gopal 1 Abstract Inhibition of cyclin-dependent kinases (CDKs) is a promising strategy for mantle cell lymphoma (MCL). We conducted a phase II study of P276-00, a small molecule inhibitor of several CDK isoforms, in patients with relapsed or refractory MCL. Although relatively well-tolerated, no objective responses were seen. Future studies with this agent should consider it in new schedules or combined with other treatments. Introduction: Overexpression of cyclin D1 is a hallmark feature of mantle cell lymphoma (MCL). Many of the onco- genic effects of cyclin D1 are mediated through cyclin-dependent kinases (CDKs). P276-00 is a potent small molecule inhibitor of CDK4-D1, CDK1-B, and CDK9-T, with promising activity in preclinical models. In phase I studies of P276-00 in patients with refractory solid neoplasms, it was well-tolerated with a mild trend toward single-agent ef- ficacy. Patients and Methods: A phase II study of P276-00 was conducted in patients with relapsed or refractory MCL at the recommended dose of 185 mg/m2/day from days 1 to 5 of a 21-day cycle. Thirteen patients were enrolled in the present study. Results: Of the 13 patients, 11 experienced disease progression, 1 patient was withdrawn because of an adverse event (AE), and 1 patient died. Also, 11 patients (84.6%) exp