Abstract CT215: CHRONOS-1: Open-label, uncontrolled phase II trial of intravenous phosphatidylinositol-3 kinase alpha/delta inhibitor copanlisib in patients with relapsed, indolent Non-Hodgkin's lymphomas (iNHL)
Authors: Dreyling Martin , Giurescu Marius , Grunert Julia , Fittipaldi Felipe , Cupit Lisa , Childs Barrett H. 
Published: August 2015

Abstract
Background: Copanlisib is a novel pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with potent preclinical inhibitory activity against both PI3K-δ and PI3K-α isoforms. Results from a phase II study of copanlisib in 67 patients with relapsed/refractory indolent or aggressive lymphoma have been reported, with a promising overall response rate for 53% seen for patients in the indolent lymphoma group (Dreyling et al., ASH 2014; Dreyling et al., ENA 2014). Enrollment in an expansion cohort of 120 patients with indolent lymphoma has been initiated. The objective of the study is to evaluate the efficacy and safety of copanlisib in patients with indolent B-cell NHL relapsed after or refractory to standard therapy.
Methods: In this study (NCT01660451), patients meeting the following criteria will be eligible for enrollment: histologically confirmed diagnosis of indolent B-cell NHL, with follicular lymphoma (FL) grade 1-2-3a, marginal zone lymphoma (MZL; splenic, nodal, or extra-nodal), small lymphocytic lymphoma (SLL) with absolute lymphocyte count &lt; 5 × 109/L at the time of diagnosis and at study entry, or lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), and who have relapsed or are refractory after ≥ 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen; patients must have received Rituximab and alkylating agents). Patients will receive 60 mg of copanlisib administered intravenously on days 1, 8 and 15 of a 28-day cycle. Dose reductions due to toxicities to 45 mg and 30 mg will be allowed. Patients will be followed until disease progression or intolerable toxicity. Radiologic tumor assessment will be performed every 2 cycles. Adverse events will be collected and graded using NCI-CTCAE v4. The primary endpoint will be overall objective response rate (ORR), defined as a complete response (CR) or partial response (PR) up to 16 weeks after the last patient fully evaluable for the primary endpoint started treatment. Secondary objectives include duration of response (DOR), progression-free survival (PFS), overall survival (OS), and quality of Life questionnaire (FACT-Lym symptoms subscale and total score) at week 16. Assuming a one-sided alpha of 0.025, 90% power and a true ORR of 75%, a total of 120 patients will be required.
The trial is currently enrolling patients.
Citation Format: Martin Dreyling, Marius Giurescu, Julia Grunert, Felipe Fittipaldi, Lisa Cupit, Barrett H. Childs. CHRONOS-1: Open-label, uncontrolled phase II trial of intravenous phosphatidylinositol-3 kinase alpha/delta inhibitor copanlisib in patients with relapsed, indolent Non-Hodgkin's lymphomas (iNHL). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT215. doi:10.1158/1538-7445.AM2015-CT215