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Introduction:Copanlisib, a pan-class I phosphatidylinositol 3-kinase inhibitor, is approved in the US for the treatment of patients (pts) with relapsed follicular lymphoma (FL) who have received ≥2 prior systemic therapies; it also has Breakthrough Therapy designation for pts with relapsed marginal zone lymphoma who have received ≥2 prior therapies. The Phase II CHRONOS-1 study in pts with indolent lymphoma treated with copanlisib (NCT01660451; Part B) demonstrated an objective response rate of 59.2% with manageable safety and low rates of severe adverse events (AEs) (Dreyling M et al. J Clin Oncol 2017). We report pooled safety data from 8 Phase I and II studies of pts with hematologic malignancies following long-term treatment with copanlisib.

Zinzani: IMMUNE DESIGN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANOFI: Consultancy; CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PORTOLA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; VERASTEM: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Santoro:Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Takeda: Speakers Bureau; Abb-Vie: Speakers Bureau; Sandoz: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; MSD: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Roche: Speakers Bureau. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Follows:AZ: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Lenz:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Agios: Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Employment, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy. Kim:Celltrion: Research Funding; Mundipharma: Research Funding; J&J: Research Funding; Roche: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; Donga: Research Funding. Panayiotidis:Bayer: Other: Support of clinical trial. Demeter:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol- Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Angelini: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Morschhauser:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Munoz:Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Pharmacyclics LLC an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Kite Pharma: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Portola: Research Funding; Incyte: Research Funding. Miriyala:Bayer HealthCare Pharmaceuticals, Inc.: Employment. Benson:Bayer HealthCare Pharmaceuticals, Inc.: Employment. Garcia-Vargas:Bayer Healthcare Pharmaceuticals, Inc.: Employment. Childs:Bayer Healthcare Pharmaceuticals, Inc.: Employment. Dreyling:Novartis: Other: Scientific advisory board; Celgene: Other: Scientific advisory board, Research Funding, Speakers Bureau; Gilead: Other: Scientific advisory board, Speakers Bureau; Janssen: Other: Scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Other: Scientific advisory board, Research Funding; Roche: Other: Scientific advisory board, Research Funding, Speakers Bureau; Sandoz: Other: Scientific advisory board; Acerta: Other: Scientific advisory board; Bayer: Other: Scientific advisory board, Speakers Bureau.Copanlisib is approved in the U.S. for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies and received U.S. FDA Breakthrough Designation in May 2019 for the treatment of adult patients with relapsed marginal zone lymphoma (MZL) who have received at least 2 prior therapies. We present here Phase I and II clinical trial data of patients with a range of hematological malignancies, including FL and MZL, treated with copanlisib.

Zinzani: Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leppä:Roche: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Bayer: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy. Follows:Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Lenz:Celgene Corp.: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Novartis: Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding. Demeter:Novartis: Consultancy; BMS: Consultancy; Aramis Pharma: Consultancy; Pfizer: Consultancy; Roche: Consultancy; Angelini: Consultancy; Amgen: Consultancy. Morschhauser:Janssen: Other: Scientific Lectures; Roche: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Rodrigues:Bayer: Employment. Reeves:Joule INC: Employment; Bayer: Consultancy. Hiemeyer:Bayer: Employment. Miriyala:Bayer: Employment. Garcia-Vargas:Bayer: Employment. Childs:Bayer: Employment. Dreyling:Sandoz: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction:We previously reported that treatment of patients with relapsed or refractory indolent B-cell lymphoma with the pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor copanlisib resulted in durable responses with a manageable safety profile (Dreyling et al., J Clin Oncol35:3898-3905, 2017). Copanlisib is administered intravenously on an intermittent schedule and two of the most commonly reported adverse events are infusion-related transient elevations in blood glucose and blood pressure. Patients with a medical history of diabetes mellitus or hypertension were allowed to enroll in the CHRONOS-1 study if these conditions were well controlled. We report here on the outcomes for these subsets of patients.

Introduction:As demonstrated in the phase II CHRONOS-1 trial, the pan-class I PI3K inhibitor copanlisib, with predominant activity against PI3K-α and PI3K-δ isoforms, is highly active (objective response rate [ORR] 59.2%) in the treatment of patients with relapsed or refractory indolent B-cell lymphoma. At the time of the primary analysis (cutoff June 22, 2016; median safety follow-up of 24 weeks) the safety profile was characterized by low rates of severe elevated hepatic transaminases, diarrhea or inflammatory events, as well as low rates of opportunistic infections, fatal infections or other fatal serious adverse events. We conducted further safety and efficacy analyses based on a data cutoff on February 20, 2017 (8 months after the primary analysis) and the results are presented here.

Introduction:Copanlisib is a pan-Class I PI3K inhibitor with predominant activity against PI3K-α and PI3K-δ isoforms. It has been studied in indolent and aggressive non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (Patnaik et al., Anns Oncol2016, 27:1928-40; Dreyling et al. Anns Oncol2017, in press; Dreyling et al. ICML 2017); including a total of 168 patients with indolent NHL (iNHL). Late-onset adverse events (AE) have been reported with oral PI3K inhibitors (e.g. late-onset severe diarrhea leading to colitis). We therefore examined whether the intravenous intermittent weekly dosing of copanlisib (3 weeks on and 1 week off) influences the incidence, severity and timing of adverse events (AEs) for patients with iNHL being treated with copanlisib monotherapy.