{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:31:58Z","timestamp":1787509918810,"version":"build-2736575974"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) are rare soft tissue sarcomas with poor prognoses. Although mucin 16 (MUC16) and its soluble form, cancer antigen 125 (CA125), are established as biomarkers and therapeutic targets in ovarian cancer, emerging data suggest MUC16 may also be expressed in ES and MRT. In this study, we present a patient with ES, who demonstrated a response to ubamatamab, a novel bispecific T-cell engager (MUC16xCD3), and analyze treatment resistance after disease progression. Additionally, we examine MUC16 expression across pediatric and adolescent and young adult (AYA) sarcomas, to evaluate the frequency of this target and explore the broader application of ubamatamab in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>We performed a retrospective clinical case review and immunohistochemical analysis of pediatric and AYA (0-25 years) sarcoma samples from 2015 to 2021, evaluating MUC16 expression using anti-CA125 immunohistochemistry (IHC) on the DAKO Omnis platform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>A 23-year-old female patient with multiply relapsed metastatic ES, harboring MUC16 expression by IHC and elevated serum CA125, received intravenous ubamatamab (250 mg) once per week as part of a single patient study. After 11 weeks of ubamatamab, a RECIST v1.1 partial response was demonstrated, along with serum CA125 normalization, lasting 43 weeks. During the initial step-up dosing, the patient experienced grade 2 cytokine release syndrome. Treatment-emergent adverse events included grade 2 pleural effusion, pericardial effusion, and palmar-plantar erythrodysesthesia, all resolving without intervention. IHC analysis of retrospective samples showed positive MUC16 staining in six of eight (75%) ES and two of four (50%) MRT samples, with no immunoreactivity observed in other pediatric\/AYA sarcoma subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      MUC16 is frequently detected in ES and MRTs. Ubamatamab is an encouraging anti-MUC16 therapy, demonstrating clinical efficacy. Ongoing trials (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT06444880\">NCT06444880<\/jats:ext-link>\n                      ) are evaluating ubamatamab in other rare MUC16-positive tumors.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00404","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T19:59:09Z","timestamp":1754078349000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Mucin 16\u2013Directed Therapy in Pediatric Sarcomas: Case Evidence of Ubamatamab Efficacy in Epithelioid Sarcoma and Its Implications for Other Sarcoma Subtypes"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7379-3439","authenticated-orcid":true,"given":"Denise M.","family":"Connolly","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6512-1004","authenticated-orcid":true,"given":"Gabriel","family":"Revon-Rivi\u00e8re","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada"},{"name":"Department of Pediatric Oncology, Timone Children's Hospital, APHM, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Chami","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pathology and Laboratory Medicine, The Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Mills","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada"},{"name":"Division of Pediatric Hematology and Oncology, McMaster Children's Hospital, Hamilton, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-5939","authenticated-orcid":true,"given":"Ailish C.","family":"Coblentz","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-0924","authenticated-orcid":true,"given":"Thomas S.","family":"Uldrick","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc, Tarrytown, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Knorr","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc, Tarrytown, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc, Tarrytown, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dobosz","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc, Tarrytown, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumreen","family":"Jalal","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc, Tarrytown, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8852-1104","authenticated-orcid":true,"given":"Sarah","family":"Cohen-Gogo","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-1108","authenticated-orcid":true,"given":"Daniel A.","family":"Morgenstern","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_9_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S289544"},{"key":"e_1_3_9_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33365"},{"key":"e_1_3_9_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181882c54"},{"key":"e_1_3_9_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24315"},{"key":"e_1_3_9_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0005"},{"key":"e_1_3_9_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001011"},{"key":"e_1_3_9_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2023.2224500"},{"key":"e_1_3_9_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-024-01365-5"},{"key":"e_1_3_9_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyh027"},{"key":"e_1_3_9_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-009-0678-1"},{"key":"e_1_3_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.100821"},{"key":"e_1_3_9_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS5632"},{"key":"e_1_3_9_14_2","volume-title":"A Phase 1\/2 Study of REGN4018 (A MUC16xCD3 Bispecific Antibody) Administered Alone or in Combination with Cemiplimab in Patients with Recurrent Ovarian Cancer or Other Recurrent MUC16+ Cancers","author":"Regeneron Pharmaceuticals","unstructured":"Regeneron Pharmaceuticals: A Phase 1\/2 Study of REGN4018 (A MUC16xCD3 Bispecific Antibody) Administered Alone or in Combination with Cemiplimab in Patients with Recurrent Ovarian Cancer or Other Recurrent MUC16+ Cancers. clinicaltrials.gov; 2024. Report No.: NCT03564340. https:\/\/clinicaltrials.gov\/study\/NCT03564340"},{"key":"e_1_3_9_15_2","volume-title":"2022 CTOS Annual Meeting","unstructured":"2022 CTOS Annual Meeting. https:\/\/www.eventscribe.net\/2022\/CTOS\/fsPopup.asp?Mode=posterinfo&PosterID=526118"},{"key":"e_1_3_9_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(21)00385-X"},{"key":"e_1_3_9_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.0219"},{"key":"e_1_3_9_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1356913"},{"key":"e_1_3_9_19_2","volume-title":"Phase II Trial of Ubamatamab Alone or in Combination with Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies","author":"M.D. Anderson Cancer Center","unstructured":"M.D. Anderson Cancer Center: Phase II Trial of Ubamatamab Alone or in Combination with Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies. clinicaltrials.gov; 2024. Report No.: NCT06444880. https:\/\/clinicaltrials.gov\/study\/NCT06444880"},{"key":"e_1_3_9_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153685"},{"key":"e_1_3_9_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-3324"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T19:59:12Z","timestamp":1754078352000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":20,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1200\/PO-25-00404"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00404","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500404"}}