{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T11:55:32Z","timestamp":1793706932007,"version":"4.6.1"},"reference-count":34,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"unspecified","delay-in-days":167,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004337","name":"F. Hoffmann-La Roche Ltd","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2026,5,16]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of subcutaneously administered mosunetuzumab, a CD20xCD3 T-cell-engaging bispecific antibody, in participants with systemic lupus erythematosus (SLE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase Ib, multicentre, open-label, dose-escalation study enrolled 15 participants diagnosed with active autoantibody-positive SLE, demonstrated by an SLE Disease Activity Index 2000 (SLEDAI-2K) score \u22654 at screening. The study included two fixed-dosing dose-finding cohorts (1.6 mg or 5 mg of mosunetuzumab on day 1) and three step-up dose-escalation cohorts (day 1 dose of mosunetuzumab established by dose finding, followed by 15 mg, 45 mg or 60 mg of mosunetuzumab on day 8). The primary objective was evaluation of safety; other key objectives were evaluating the PK and PD of mosunetuzumab. Peripheral B-cell counts and T-cell phenotyping were performed using flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifteen participants were enrolled from January 2022 through December 2023. Two participants discontinued treatment due to treatment-emergent adverse events (AEs). No immune effector cell-associated neurotoxicity syndrome events or high-grade cytokine release syndrome events were reported. The frequency of grade \u22653 AEs and serious AEs was 13.3% and 6.7%, respectively. Mosunetuzumab depleted peripheral B cells below the lower limit of quantification (0.441 cells\/\u00b5L) in a dose-dependent manner. CD4+ and\u2009CD8+ T-cell activation occurred across all tested doses. SLEDAI-2K scores improved, especially among participants with higher baseline SLEDAI-2K scores and those receiving higher doses. The PK profile of mosunetuzumab was consistent with that observed in the relapsed or refractory follicular lymphoma population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Mosunetuzumab demonstrated dose-dependent peripheral B-cell depletion and a safety profile consistent with prior studies in follicular lymphoma. Based on these data, mosunetuzumab is currently being evaluated in a phase II study in severe SLE (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT07598396\">NCT07598396<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05155345\">NCT05155345<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2026-002019","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:30:33Z","timestamp":1781695833000},"page":"e002019","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Phase Ib, multicentre, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneously administered mosunetuzumab in participants with systemic lupus erythematosus"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct07598396","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05155345","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05155345","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Elsa","family":"Martins","sequence":"first","affiliation":[{"name":"F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishala L","family":"Chindalore","sequence":"additional","affiliation":[{"name":"Pinnacle Research Group, LLC, Anniston, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X Rebecca","family":"Sheng","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron V","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Chen","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardik","family":"Mody","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Arjomandi","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan (Ashley)","family":"Mao","sequence":"additional","affiliation":[{"name":"Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Hassan","sequence":"additional","affiliation":[{"name":"Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Dankiewicz-Fares","sequence":"additional","affiliation":[{"name":"Jan Biziel University Hospital, Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Agachi","sequence":"additional","affiliation":[{"name":"Nicolae Testemitanu State University of Medicine and Pharmacy, Chi\u015fin\u0103u, The Republic of Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore A","family":"Omachi","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay P","family":"Garg","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William F","family":"Pendergraft","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"2026072811152131000_13.1.e002019.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.2315"},{"key":"2026072811152131000_13.1.e002019.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1100359"},{"key":"2026072811152131000_13.1.e002019.3","first-page":"929","article-title":"Mortality in patients with systemic lupus erythematosus: A meta-analysis of overall and cause-specific effects","volume":"33","author":"Lee","year":"2024","journal-title":"Lupus (Los Angel)"},{"key":"2026072811152131000_13.1.e002019.4","doi-asserted-by":"crossref","DOI":"10.1002\/acr2.70057","article-title":"Trends in Systemic Lupus Erythematous Mortality in the United States, 1999-2022","volume":"7","author":"Patel","year":"2025","journal-title":"ACR Open Rheumatol"},{"key":"2026072811152131000_13.1.e002019.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2023.02.004"},{"key":"2026072811152131000_13.1.e002019.6","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1002\/art.40512","article-title":"Brief Report: Lupus-An Unrecognized Leading Cause of Death in Young Females: A Population-Based Study Using Nationwide Death Certificates, 2000-2015","volume":"70","author":"Yen","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"2026072811152131000_13.1.e002019.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.10.013"},{"key":"2026072811152131000_13.1.e002019.8","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20246231","article-title":"B Cell Abnormalities in Systemic Lupus Erythematosus and Lupus Nephritis-Role in Pathogenesis and Effect of Immunosuppressive Treatments","volume":"20","author":"Yap","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026072811152131000_13.1.e002019.9","doi-asserted-by":"publisher","DOI":"10.1002\/art.27233"},{"key":"2026072811152131000_13.1.e002019.10","doi-asserted-by":"publisher","DOI":"10.1002\/art.34359"},{"key":"2026072811152131000_13.1.e002019.11","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220920"},{"key":"2026072811152131000_13.1.e002019.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2410965"},{"key":"2026072811152131000_13.1.e002019.13","doi-asserted-by":"crossref","unstructured":"Furie RA , Dall\u2019Era M , Vital EM , et al . Efficacy and Safety of Obinutuzumab in Active Systemic Lupus Erythematosus. N Engl J Med 2026. doi:10.1056\/NEJMoa2516150","DOI":"10.1056\/NEJMoa2516150"},{"key":"2026072811152131000_13.1.e002019.14","doi-asserted-by":"crossref","first-page":"1476859","DOI":"10.3389\/fimmu.2024.1476859","article-title":"CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives","volume":"15","author":"Zhou","year":"2024","journal-title":"Front Immunol"},{"key":"2026072811152131000_13.1.e002019.15","doi-asserted-by":"crossref","DOI":"10.1177\/2515135520927164","article-title":"CAR T-cell immunotherapy of B-cell malignancy: the story so far","volume":"8","author":"Halim","year":"2020","journal-title":"Ther Adv Vaccines Immunother"},{"key":"2026072811152131000_13.1.e002019.16","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-025-02269-w","article-title":"CAR-T cell therapy for cancer: current challenges and future directions","volume":"10","author":"Zugasti","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"2026072811152131000_13.1.e002019.17","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1583116","article-title":"CAR-T cell therapy clinical trials: global progress, challenges, and future directions from ClinicalTrials.gov insights","volume":"16","author":"Cao","year":"2025","journal-title":"Front Immunol"},{"key":"2026072811152131000_13.1.e002019.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02017-5"},{"key":"2026072811152131000_13.1.e002019.19","doi-asserted-by":"crossref","unstructured":"Muller F , Taubmann J , Bucci L , et al . CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. 2024;390:687\u2013700. doi:10.1056\/NEJMoa2308917","DOI":"10.1056\/NEJMoa2308917"},{"key":"2026072811152131000_13.1.e002019.20","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-226142"},{"key":"2026072811152131000_13.1.e002019.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00547-6"},{"key":"2026072811152131000_13.1.e002019.22","doi-asserted-by":"crossref","DOI":"10.1007\/s10238-024-01520-y","article-title":"Bispecific antibodies in clinical practice: Understanding recent advances and current place in cancer treatment landscape","volume":"25","author":"Verma","year":"2024","journal-title":"Clin Exp Med"},{"key":"2026072811152131000_13.1.e002019.23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1515\/rir-2024-0029","article-title":"Therapeutic potential of CD20\/CD3 bispecific antibodies in the treatment of autoimmune diseases","volume":"5","author":"Huang","year":"2025","journal-title":"Rheumatol Immunol Res"},{"key":"2026072811152131000_13.1.e002019.24","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1182\/blood.2024025454","article-title":"Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after \u22652 prior therapies","volume":"145","author":"Sehn","year":"2025","journal-title":"Blood"},{"key":"2026072811152131000_13.1.e002019.25","unstructured":"European Medicines Agency . Lunsumio summary of product characteristics. Available: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/lunsumio-epar-product-information_en.pdf [Accessed Dec 2025]."},{"key":"2026072811152131000_13.1.e002019.26","unstructured":"US Food and Drug Administration . Lunsumio prescribing information. Available: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761263s000lbl.pdf [Accessed Dec 2025]."},{"key":"2026072811152131000_13.1.e002019.27","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00335-7"},{"key":"2026072811152131000_13.1.e002019.28","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa4802","article-title":"Anti-CD20\/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies","volume":"7","author":"Sun","year":"2015","journal-title":"Sci Transl Med"},{"key":"2026072811152131000_13.1.e002019.29","unstructured":"US Food and Drug Administration . Guidance for industry drug-induced liver injury: premarketing clinical evaluation. 2009. Available: https:\/\/www.fda.gov\/media\/116737\/download [Accessed Mar 2026]."},{"key":"2026072811152131000_13.1.e002019.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.758"},{"key":"2026072811152131000_13.1.e002019.31","doi-asserted-by":"crossref","first-page":"109265","DOI":"10.1016\/j.clim.2023.109265","article-title":"Development of a novel, highly sensitive assay for quantification of minimal residual B cells in autoimmune disease and comparison to traditional methods across B-cell-depleting agents","volume":"248","author":"Looney","year":"2023","journal-title":"Clin Immunol"},{"key":"2026072811152131000_13.1.e002019.32","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fmed.2020.00316","article-title":"B Cell Therapy in Systemic Lupus Erythematosus: From Rationale to Clinical Practice","volume":"7","author":"Parodis","year":"2020","journal-title":"Front Med"},{"key":"2026072811152131000_13.1.e002019.33","unstructured":"Tabilas C , Gong Q , Maximov V , et al . Understanding the biology of \u201cimmune reset\u201d: defining the capabilities of various b cell depleting modalities for autoimmunity. Presented at the Autoimmunity and Autoinflammation: Translating Basic Mechanisms into Novel Therapeutic Approaches Keystone Symposium 2026; 2026:19\u201322."},{"key":"2026072811152131000_13.1.e002019.34","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1007\/s00210-025-04425-z","article-title":"CAR T cell therapy efficacy and safety in SLE: a systematic review and pooled analysis of 47 patients across 10 studies","volume":"399","author":"Sayed","year":"2026","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"}],"container-title":["Lupus Science &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/lupus-2026-002019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T18:15:31Z","timestamp":1785262531000},"score":1,"resource":{"primary":{"URL":"https:\/\/lupus.bmj.com\/lookup\/doi\/10.1136\/lupus-2026-002019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,6,17]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/lupus-2026-002019"],"URL":"https:\/\/doi.org\/10.1136\/lupus-2026-002019","relation":{},"ISSN":["2053-8790"],"issn-type":[{"value":"2053-8790","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}