{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:05:28Z","timestamp":1790643928292,"version":"4.1.0"},"reference-count":35,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Chronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. Colony-stimulating factor 1 receptor (CSF-1R)\u2013dependent macrophages promote cGVHD fibrosis, and their elimination in preclinical studies ameliorated cGVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>This phase I (phI)\/phase II (phII) open-label study (ClinicalTrials.gov identifier: NCT03604692 ) evaluated safety, tolerability, and efficacy of axatilimab in patients age \u2265 6 years with active cGVHD after \u2265 2 prior systemic therapy lines. Primary objectives in phI were to identify the optimal biologic and recommended phII dose and in phII to evaluate the overall (complete and partial) response rate (ORR) at the start of treatment cycle 7.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Forty enrolled patients (17 phI; 23 phII) received at least one axatilimab dose. In phI, a dose of 3 mg\/kg given once every 4 weeks met the optimal biologic dose definition. Two dose-limiting toxicities occurred at the 3 mg\/kg dose given once every 2 weeks. At least one treatment-related adverse event (TRAE) was observed in 30 patients with grade \u2265 3 TRAEs in eight patients, the majority known on-target effects of CSF-1R inhibition. No cytomegalovirus reactivations occurred. With the 50% ORR at cycle 7 day 1, the phII cohort met the primary efficacy end point. Furthermore, the ORR in the first six cycles, an end point supporting regulatory approvals, was 82%. Responses were seen in all affected organs regardless of prior therapy. Fifty-eight percent of patients reported significant improvement in cGVHD-related symptoms using the Lee Symptom Scale. On-target activity of axatilimab was suggested by the decrease in skin CSF-1R\u2013expressing macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Targeting profibrotic macrophages with axatilimab is a therapeutically promising novel strategy with a favorable safety profile for refractory cGVHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.22.00958","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T15:59:28Z","timestamp":1669996768000},"page":"1864-1875","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":105,"title":["Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I\/II Study"],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct03604692","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-2901","authenticated-orcid":true,"given":"Carrie L.","family":"Kitko","sequence":"first","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-0556","authenticated-orcid":true,"given":"Mukta","family":"Arora","sequence":"additional","affiliation":[{"name":"University of Minnesota Masonic Cancer Center, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-8974","authenticated-orcid":true,"given":"Zachariah","family":"DeFilipp","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-6941","authenticated-orcid":true,"given":"Mohammad Abu","family":"Zaid","sequence":"additional","affiliation":[{"name":"Indiana University Simon Cancer Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Stasi","sequence":"additional","affiliation":[{"name":"University of Alabama, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9699-1157","authenticated-orcid":true,"given":"Vedran","family":"Radojcic","sequence":"additional","affiliation":[{"name":"University of Utah Huntsman Cancer Institute, Salt Lake City, UT"},{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0432-0445","authenticated-orcid":true,"given":"Courtney B.","family":"Betts","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-1865","authenticated-orcid":true,"given":"Lisa M.","family":"Coussens","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Meyers","sequence":"additional","affiliation":[{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope","family":"Qamoos","sequence":"additional","affiliation":[{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"},{"name":"Kartos Therapeutics, Inc, Redwood City, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ordentlich","sequence":"additional","affiliation":[{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"},{"name":"Daiichi Sankyo, Inc, Basking Ridge, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Quaranto","sequence":"additional","affiliation":[{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"},{"name":"Aerovate Therapeutics, Inc, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gu","sequence":"additional","affiliation":[{"name":"Syndax Pharmaceuticals, Inc, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-9841","authenticated-orcid":true,"given":"Bruce R.","family":"Blazar","sequence":"additional","affiliation":[{"name":"Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5685-7204","authenticated-orcid":true,"given":"Trent P.","family":"Wang","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-5041","authenticated-orcid":true,"given":"Amandeep","family":"Salhotra","sequence":"additional","affiliation":[{"name":"City of Hope Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iskra","family":"Pusic","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Saint Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-5604","authenticated-orcid":true,"given":"Madan","family":"Jagasia","sequence":"additional","affiliation":[{"name":"Iovance Biotherapeutics, San Carlos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2600-6390","authenticated-orcid":true,"given":"Stephanie J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.10.021"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.10.018"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2013.70"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.7212"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004941"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-350249"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.11.018"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-464198"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.07.001"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-11-319509"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-775767"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1177\/2040620720977039"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-07-793786"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012021"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2033122"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2021.08.017"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.09.023"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703472"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-686618"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75935"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-758854"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.02.001"},{"key":"b23","first-page":"P402","volume":"4","author":"Ordentlich P","year":"2016","journal-title":"J Immunother Cancer"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.12.001"},{"key":"b25","first-page":"P505","volume":"5","author":"Tiessen R","year":"2016","journal-title":"J Immunother Cancer"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2020-CT149"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.02.025"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1053\/bbmt.2002.v8.pm12234170"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.05.016"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0257-y"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd4550"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-563544"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000918"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.1038\/nri1412"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133909"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.22.00958","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T14:15:42Z","timestamp":1681308942000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.22.00958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,4,1]]}},"alternative-id":["10.1200\/JCO.22.00958"],"URL":"https:\/\/doi.org\/10.1200\/jco.22.00958","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,1]]},"assertion":[{"value":"2022-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-01","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}