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This phase I multicenter investigator-sponsored study evaluated safety and efficacy of copanlisib plus nivolumab in 27 adults with relapsed/refractory RT or tNHL. Escalating copanlisib doses with fixed nivolumab showed diarrhea and anemia as common adverse events; two patients at the DL2 dose level experienced dose-limiting toxicities. The maximum tolerated dose was 45 mg. Overall response rate was 46%, including stronger activity in transformed follicular lymphoma (ORR 67%) than in RT (ORR 31%).",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/article-non-hodgkin-lymphoma-safety-and-efficacy-of-the-combination-of-copanlisib-and-nivolumab-in-patients-with-richters-transformation-or-transformed-non-hodgkin-lymphoma-results-from-a-phase-i-trial/448213/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/article-non-hodgkin-lymphoma-safety-and-efficacy-of-the-combination-of-copanlisib-and-nivolumab-in-patients-with-richters-transformation-or-transformed-non-hodgkin-lymphoma-results-from-a-phase-i-trial/448213.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main purpose of this phase I multicenter study?","Question",{"text":112,"@type":113},"To evaluate the safety and efficacy of copanlisib combined with nivolumab in adults with Richter’s transformation or transformed non-Hodgkin lymphoma.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were copanlisib and nivolumab administered in the treatment regimen?",{"text":117,"@type":113},"Copanlisib was given as IV doses on days 1, 8, and 15 with escalating dose levels, combined with nivolumab 240 mg IV on days 1 and 15 of a 28-day cycle.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key efficacy results and how did they differ by patient subgroup?",{"text":121,"@type":113},"The overall response rate was 46%. Patients with transformed follicular lymphoma had an ORR of 67%, while patients with Richter’s transformation had an ORR of 31%.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},448213,1790766275,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","ARTICLE-Non-Hodgkin Lymphoma  \nSafety and efficacy of the combination of copanlisib and nivolumab in patients with Richter’s transformation or transformed non-Hodgkin lymphoma: results from a  \nphase I trial  \nGeoffrey Shouse,1 Canping Chen,2 Alexandra Muir,1 Leslie Popplewell,1 Tanya Siddiqi,1 Jasmine Zain,3 Alex F. Herrera,1 Olga Danilova,1 Carly Roleder,1 Lili Wang,1 Stephen E. F. Spurgeon,3 Adam S. Kittai,4 Lu Chen,1 Zheng Xia,2 Matthew S. Davids5 and Alexey V. Danilov1  \n1City of Hope National Medical Center, Duarte, CA; 2Oregon Health and Science University, Portland, OR; 3 Memorial Sloan Kettering Cancer Center, New York, NY; 4 Icahn School of Medicine at Mount Sinai, New York, NY and 5 Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, USA  \nCorrespondence: A.V. Danilov  \n[adanilov@coh.org](adanilov@coh.org)  \nReceived: November 11, 2024.  \nAccepted: June 20, 2025.  \nEarly view: July 3, 2025.  \n[https://doi.org/10.3324/haematol.2024.286945](https://doi.org/10.3324/haematol.2024.286945)  \n©2026 Ferrata Storti Foundation  \nPublished under a CC BY-NC license   \nAbstract  \nDespite advances in targeted and cellular therapies, outcomes for patients with Richter’s transformation (RT) and transformed non-Hodgkin lymphoma (tNHL) remain dismal. In this report of a phase I multicenter investigator-sponsored study we describe the safety and efficacy of the combination of copanlisib, a selective, small molecule inhibitor of phosphoinositide-3-kinase, and nivolumab, an antibody against programmed cell death protein 1. Twenty-seven adult patients with relapsed and/or refractory RT or tNHL were treated with escalating doses of copanlisib IV on days 1, 8, and 15 (dose level [DL] 1-45 mg, DL2-60 mg) combined with nivolumab 240 mg IV on days 1 and 15 of a 28-day cycle. Three dose-limiting toxicities occurred in two patients treated at DL2, hence 45 mg was determined to be the maximum tolerated dose and utilized in the expansion cohort. The most common treatment-related adverse events were diarrhea and anemia. All patients went off protocol, predominantly because of progressive disease and adverse events (67% and 26% of patients, respectively) . The overall response rate (ORR) was 46% . Patients with transformed follicular lymphoma had an ORR of 67%(2 complete responses), with median progression-free survival of 4.4 months (95% confidence interval: 1.4-12.2) . Patients with RT had an ORR of 31%(2 complete responses) with a median progression-free survival of 2.0 months (95% confidence interval: 0.7- 4.9) . Treatment resulted in downregulation of MYC and NFkB pathways in malignant B cells. Responding RT patients exhibited sustained activation of interferon-a and interferon-γ signaling pathways in CD4+ and CD8+ T cells. Overall, treatment with copanlisib and nivolumab demonstrated manageable toxicity and promising clinical efficacy in tNHL patients.  \nIntroduction  \nTransformation from indolent non-Hodgkin lymphoma (NHL) to aggressive lymphoma (most commonly diffuse large B-cell lymphoma [DLBCL]) represents an entity that is challenging to treat. It can occur in any indolent NHL including follicular lymphoma (FL), lymphoplasmacytic lymphoma, marginal zone lymphoma and small lymphocytic lymphoma/ chronic lymphocytic leukemia (CLL) . Transformation occurs at a rate of 0.5-3% per year with the median survival ranging from 16-60 months depending on the subtype 1-4 There is variability in survival due to differences in the definition of transformation across studies as well as lack of a uniform approach to treatment.5 Although there is no established  \nstandard of care, patients with transformed NHL (tNHL) are most often treated similarly to those with aggressive NHL histology.5  \nThe prognosis of patients who develop Richter’s transformation (RT) -the progression of CLL, most commonly to DLBCL-is particularly poor with a median survival of only 4-12 months.6,7 RT occurs at a rate of ~0.5% per year, affecting 2-10% of CLL patients","cbCaih5qyO5nxdYH","https://ap.wps.com/l/cbCaih5qyO5nxdYH","pdf",1313939,12,"English","# Abstract\n## Introduction","[{\"question\":\"What was the main purpose of this phase I multicenter study?\",\"answer\":\"To evaluate the safety and efficacy of copanlisib combined with nivolumab in adults with Richter’s transformation or transformed non-Hodgkin lymphoma.\"},{\"question\":\"How were copanlisib and nivolumab administered in the treatment regimen?\",\"answer\":\"Copanlisib was given as IV doses on days 1, 8, and 15 with escalating dose levels, combined with nivolumab 240 mg IV on days 1 and 15 of a 28-day cycle.\"},{\"question\":\"What were the key efficacy results and how did they differ by patient subgroup?\",\"answer\":\"The overall response rate was 46%. Patients with transformed follicular lymphoma had an ORR of 67%, while patients with Richter’s transformation had an ORR of 31%.\"}]","ARTICLE - Non-Hodgkin Lymphoma - Safety and efficacy of the combination of copanlisib and nivolumab in patients with Richter’s transformation or transformed non-Hodgkin lymphoma - results from a phase I trial | PDF",1790726078]