{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:54:28Z","timestamp":1785405268010,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011928","name":"Swiss Cancer Research","doi-asserted-by":"publisher","award":["KFS-4727-02-2019"],"award-info":[{"award-number":["KFS-4727-02-2019"]}],"id":[{"id":"10.13039\/501100011928","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BAYER"},{"id":[{"id":"https:\/\/ror.org\/01qwdc951","id-type":"ROR","asserted-by":"publisher"}]},{"name":"AbbVie"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: This phase I trial aimed to assess the safety and preliminary activity of the combination of copanlisib with venetoclax in previously treated patients with B-cell non-Hodgkin lymphoma, excluding mantle-cell lymphoma patients. Methods: Intravenous copanlisib on days 1, 8, and 15 and oral venetoclax once daily (starting on day 2 of cycle 1, continuously) were administered in 28-day cycles up to a maximum of 12 cycles. Starting doses were 600 mg of venetoclax and 60 mg of copanlisib. Results: A total of seven patients were enrolled. The first two presented dose-limiting toxicities, five additional patients were treated at a lower dose level (45 mg of copanlisib and 400 mg of venetoclax), with no dose-limiting toxicities observed among three evaluable patients. The most frequent treatment-related adverse event of grade 3 or higher was neutropenia (n = 3), followed by thrombocytopenia (n = 2) and hypertension (n = 2). Four treatment-related serious adverse events occurred, including grade 3 febrile neutropenia in one patient and respiratory infections in three patients. Two patients had complete responses, and two had partial responses. Transcriptomic analysis of lymphoma samples showed enrichment of genes coding for proteins involved in B-cell receptor signaling in responding patients. The study was terminated prematurely due to a decision by the pharmaceutical company. Conclusions: Due to the limited sample size, no definite conclusions regarding safety or activity of the combination can be drawn. The two drugs could not be combined at their respective single-agent doses. Responses were observed in heavily pretreated patients. Transcriptomic analyses suggested a possible association between response and B-cell receptor signaling, which warrants further investigation.<\/jats:p>","DOI":"10.3390\/cancers18111764","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:57:43Z","timestamp":1779962263000},"page":"1764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase Ib Trial of Copanlisib in Combination with Venetoclax in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma\u2014SAKK 66\/18 Trial"],"prefix":"10.3390","volume":"18","author":[{"given":"Maria Cristina","family":"Pirosa","sequence":"first","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6500 Bellinzona, Switzerland"},{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"},{"name":"Faculty 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-1088","authenticated-orcid":false,"given":"Nicolas","family":"Mach","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Gen\u00e8ve, 1205 Gen\u00e8ve, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Zenz","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsspital Z\u00fcrich, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Holer","sequence":"additional","affiliation":[{"name":"Competence Center of SAKK, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4606-0637","authenticated-orcid":false,"given":"Luciano","family":"Cascione","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6500 Bellinzona, Switzerland"},{"name":"SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9551-7122","authenticated-orcid":false,"given":"Eleonora","family":"Cannas","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e4mi","family":"Sch\u00e4r","sequence":"additional","affiliation":[{"name":"Competence Center of SAKK, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5522-6109","authenticated-orcid":false,"given":"Emanuele","family":"Zucca","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6500 Bellinzona, Switzerland"},{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5637-8983","authenticated-orcid":false,"given":"Francesco","family":"Bertoni","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6500 Bellinzona, Switzerland"},{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Stathis","sequence":"additional","affiliation":[{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.2022015851","article-title":"The International Consensus Classification of Mature Lymphoid Neoplasms: A report from the Clinical Advisory Committee","volume":"140","author":"Campo","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World 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