Phase II study of copanlisib,a PI3K inhibitor,in relapsed or refractory,indolent or aggressive lymphoma |
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| Institution: | 1. Department of Medicine III, University Hospital, LMU Munich, Munich, Germany;2. Hematology Department, Hôpital Claude Huriez, Unité GRITA, Lille University, Lille;3. Department of Hematology and Cellular Therapy, University Hospital of Bordeaux, Pessac, France;4. Department of Clinical and Experimental Hematology, Jules Bordet Institute (Free University of Brussels – ULB), Brussels, Belgium;5. Department of Clinical and Experimental Haematology, The Royal Marsden Hospital, Sutton, UK;6. Division of Hematology, Jewish General Hospital, Montreal, Canada;7. Department of Haematology, University Hospital Leuven, Leuven, Belgium;8. Department of Haemato-oncology, The Christie NHS Foundation Trust, Manchester, UK;9. Department of Hemato-oncology, APHP-Hôpital Saint-Louis, Paris;10. Diderot University, Sorbonne Paris Cité, Paris;11. EA3788, Descartes University, Paris, France;12. Department of Oncology and Hematology, Città della Salute e della Scienza di Torino, Torino, Italy;13. Bayer AG, Berlin, Germany;14. Bayer HealthCare Pharmaceuticals, Inc., Whippany, USA;15. Bayer SA, São Paulo, Brazil;16. Department of Hematology and Oncology, Policlinico S. Orsola-Malpighi, Bologna, Italy |
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| Abstract: | BackgroundCopanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms.Patients and methodsThis phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis.ResultsThirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2–138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0–874) and 70 days (range 0–897), respectively; median duration of response was 390 days (range 0–825) and 166 days (range 0–786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression.ConclusionIntravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing.This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A). |
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