{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:52:02Z","timestamp":1787964722368,"version":"build-2784847793"},"reference-count":4,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese National Major Project for New Drug Innovation","award":["2015ZX09501008, 2017ZX09304015"],"award-info":[{"award-number":["2015ZX09501008, 2017ZX09304015"]}]},{"name":"CAMS Innovation Fund for Medical Science","award":["CAMS Innovation Fund for Medical Science"],"award-info":[{"award-number":["CAMS Innovation Fund for Medical Science"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15\u2009years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-na\u00efve, CD20-positive DLBCL patients aged 18\u201380\u2009years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1-year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], \u2212 3.59 to 6.32,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.608) which falls within the pre-defined equivalence margin of \u00b1 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%,\n                    <jats:italic>p<\/jats:italic>\n                    = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.chinadrugtrials.org.cn\">http:\/\/www.chinadrugtrials.org.cn<\/jats:ext-link>\n                    on 26 August 2015 [#CTR20150583].\n                  <\/jats:p>","DOI":"10.1186\/s13045-020-00871-9","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T11:04:48Z","timestamp":1587035088000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell 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CHOP Chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-Cell lymphoma. The N Engl J Med. 2002;346(4):235\u201342.","journal-title":"The N Engl J Med."},{"issue":"3","key":"871_CR2","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1080\/19420862.2019.1578147","volume":"11","author":"Y Xu","year":"2019","unstructured":"Xu Y, Xie L, Zhang E, Gao W, Wang L, Cao Y, et al. Physicochemical and functional assessments demonstrating analytical similarity between rituximab biosimilar HLX01 and the MabThera\u00ae. MAbs. 2019;11(3):606\u201320.","journal-title":"MAbs."},{"issue":"11","key":"871_CR3","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/S1470-2045(11)70235-2","volume":"12","author":"M Pfreundschuh","year":"2011","unstructured":"Pfreundschuh M, Kuhnt E, Tr\u00fcmper L, \u00d6sterborg A, Trneny M, Shepherd L, et al. 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Blood. 2004;104(11):157.","journal-title":"Blood."}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-020-00871-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13045-020-00871-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-020-00871-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T21:42:15Z","timestamp":1618522935000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-020-00871-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":4,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["871"],"URL":"https:\/\/doi.org\/10.1186\/s13045-020-00871-9","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,16]]},"assertion":[{"value":"11 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The protocol was developed by the sponsor of the study, Shanghai Henlius Biotech, Inc. The study protocol was reviewed and approved by the relevant independent ethics committee at each participating study center. Written informed consent was obtained from all study participants prior to screening. Data were collected by the site investigators who vouch for the completeness and accuracy of the data and the fidelity of the trial to the protocol. The sponsor analyzed the data. The study was conducted in accordance with the Declaration of Helsinki, Guideline for Good Clinical Practice, and applicable national and local regulations for clinical trials.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CMM, JCC, KC, AL, EL, and XZ are employees of Shanghai Henlius Biotech, Inc. All other authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38"}}