1000PD - Copanlisib treatment in patients with relapsed or refractory indolent B-cell lymphoma: Subgroup analyses from the CHRONOS-1 study

Date 11 September 2017
Event ESMO 2017 Congress
Session Haematological malignancies
Topics Lymphomas
Haematologic Malignancies
Presenter Mariano Provencio Pulla
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors M. Provencio Pulla1, A. Santoro2, L. Mollica3, S. Leppä4, G. Follows5, G. Lenz6, W.S. Kim7, A. Nagler8, P. Panayiotidis9, J. Demeter10, M. Özcan11, M. Kosinova12, K. Bouabdallah13, F. Morschhauser14, T. Ishida15, L. Huang16, J. Garcia-Vargas17, B.H. Childs17, P.L. Zinzani18, M. Dreyling19
  • 1Servicio De Oncología Médica, Hospital Universitario Puerta de Hierro, 28222 - Madrid/ES
  • 2Department Of Oncology And Hematology, Istituto Clinico Humanitas, 20089 - Rozzano/IT
  • 3Department Of Hematology, Hôpital Maisonneuve-Rosemont-Montreal, Montreal/CA
  • 4Department Of Oncology, Helsinki University Central Hospital, 00029 - Helsinki/FI
  • 5Department Of Haematology, Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital |, Cambridge/GB
  • 6Translational Oncology, University Hospital Münster, Münster/DE
  • 7Division Of Hematology And Oncology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul/KR
  • 8Hematology Division, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer/IL
  • 9Molecular Hematology Laboratory, 1st Department Of Propaedeutic Medicine, National and Kapodistrian University of Athens, School of Medicine, Laikon General Hospital, Athens/GR
  • 10First Department Of Internal Medicine, Division Of Haematology, Semmelweis University, Budapest/HU
  • 11Department Of Hematology, Ankara University School of Medicine, Ankara/TR
  • 12Department Of Hematology, GAUZKO "Kemerovo Regional Clinical Hospital", 650066 - Kemerovo/RU
  • 13Service D'hématologie Et De Thérapie Cellulaire, University Hospital of Bordeaux, Pessac/FR
  • 14Department Of Hematology, CHRU - Hôpital Claude Huriez, Lille/FR
  • 15Development Operations, Bayer SA, São Paulo/BR
  • 16Clinical Statistics, Bayer HealthCare Pharmaceuticals USA, 07981 - Whippany/US
  • 17Clinical Development, Bayer HealthCare Pharmaceuticals Inc., 07981 - Whippany/US
  • 18Institute Of Hematology “l. E A. Seràgnoli”, University of Bologna, Bologna/IT
  • 19Medizinische Klinik Und Poliklinik Iii, Klinikum der Universität München-Grosshadern, Munich/DE



Copanlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant activity against PI3K-α and PI3K-δ isoforms, has recently been shown to achieve a 59% objective tumor response rate (ORR) in a phase II study in patients with relapsed or refractory (r/r) indolent B-cell lymphoma. We report here the results of subgroup analyses conducted based on demographic and baseline disease characteristics.


Patients with indolent B-cell non-Hodgkin lymphoma (4 subtypes: follicular [FL], marginal zone [MZL], small lymphocytic [SLL] and lymphoplasmacytoid/Waldenström macroglobulinemia [LPL-WM]) and r/r to ≥ 2 prior lines of treatment were eligible. Previous treatment had to include rituximab and an alkylating agent. Copanlisib (60 mg, I.V.) was administered intermittently on days 1, 8 and 15 of a 28-day cycle. The primary efficacy endpoint was ORR as assessed per independent radiologic review (Cheson et al. 2007).


The full analysis set comprised 142 patients, of which 141 patients had indolent lymphoma (FL/MZL/SLL/LPL-WM: 104/23/8/6). ORR per histological subgroup was 58.7%/69.6%/75.0%/16.7%, respectively. ORR based on demographics were generally consistent across categories. Likewise, there were no major differences in ORR between any of the baseline disease characteristics and prior therapy subgroups with regards to ECOG PS (0 [58.8%] vs. ≥ 1 [59.7%]), longest diameter of baseline lesion (< 7cm [59.8%] vs. ≥ 7cm [59.1%]), received prior bendamustine (yes [62.7%] vs. no [56.6%]), number of prior therapies (< 4 [59.8%] vs. ≥ 4 [57.5%]), or refractoriness to last regimen (yes [60.5%] vs. no [57.1%]). Median duration of response (DOR) by tumor histology for the subgroups with ≥ 10 responders was 370 days (range 33-687) for FL patients and had not yet been reached for MZL patients (2 of 16 responders having progressed).


Objective response rates were consistently high in patients with r/r indolent B-cell lymphoma treated with copanlisib with the exception of LPL-WM patients. There were no major differences in the ORR between any of the baseline disease characteristics and prior therapy subgroups, confirming the robustness of the primary efficacy endpoint.

Clinical trial identification


Legal entity responsible for the study

Bayer AG


Bayer AG


T. Ishida: Employment: Bayer SA. L. Huang, J. Garcia-Vargas, B.H. Childs: Employment: Bayer HealthCare Pharmaceuticals Inc. M. Dreyling: Advisory boards: Bayer, Gilead Honoraria: Bayer, Gilead. All other authors have declared no conflicts of interest.