Julia Grunert

Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial.

BACKGROUND The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. METHODS In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. RESULTS Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. CONCLUSION Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone.

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)

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 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-Hodgkin9s 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