{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T07:03:33Z","timestamp":1784963013501,"version":"3.55.0"},"reference-count":25,"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>\n                      Neuregulin-1 (\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      ) fusions are rare but actionable oncogenic drivers in solid tumors. Seribantumab is a fully human anti-HER3 IgG2 monoclonal antibody. In this report, we present the antitumor activity and safety data of seribantumab from the CRESTONE study (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\/NCT04383210\">NCT04383210<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      This was a prospective phase II clinical study in which patients with advanced solid tumors harboring an\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      fusion received seribantumab at a dose of 3,000 mg intravenously once weekly. The primary end point was objective response rate (ORR) by RECIST v1.1. Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). The study was terminated before full enrollment because of sponsor decision, unrelated to safety or efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 54 patients with nine different tumor types featuring 19 different\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      fusion partners were enrolled. For the 29 patients included in the primary efficacy analysis, the investigator-assessed ORR was 34.5% (95% CI, 17.9 to 54.3), with a DCR of 79% (95% CI, 60 to 92). The median PFS was 5.4 (95% CI, 3.9 to 10.8) months; the median OS was 20.3 (95% CI, 10.2 to not reached) months. In patients with non\u2013small cell lung cancer, eight of 22 achieved response (ORR, 36.4%). Adverse events (AEs) were mostly grade 1 or 2. The most common treatment-related AEs were diarrhea (39%), fatigue (32%), and nausea (22%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      These results support the antitumor activity and safety of seribantumab in patients with advanced solid tumors harboring\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      fusions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00221","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T20:59:19Z","timestamp":1766437159000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["CRESTONE: A Phase II Study of the Efficacy and Safety of the HER3 Monoclonal Antibody, Seribantumab, in Solid Tumors With Neuregulin-1 (\n                    <i>NRG1<\/i>\n                    ) Fusions"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"nct04383210","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-1010","authenticated-orcid":true,"given":"Tejas","family":"Patil","sequence":"first","affiliation":[{"name":"University of Colorado Cancer Center, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7373-3916","authenticated-orcid":true,"given":"Jessica J.","family":"Lin","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parneet K.","family":"Cheema","sequence":"additional","affiliation":[{"name":"William Osler Health System, Calgary, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-4232","authenticated-orcid":true,"given":"Daniel R.","family":"Carrizosa","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute\/Atrium Health, Charlotte, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-7722","authenticated-orcid":true,"given":"Mark E.","family":"Burkard","sequence":"additional","affiliation":[{"name":"University of Iowa Health Care Holden Comprehensive Cancer Center, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-909X","authenticated-orcid":true,"given":"Yasir Y.","family":"Elamin","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4246-9344","authenticated-orcid":true,"given":"Jayesh","family":"Desai","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7550-2094","authenticated-orcid":true,"given":"Jyoti D.","family":"Patel","sequence":"additional","affiliation":[{"name":"Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-615X","authenticated-orcid":true,"given":"Misako","family":"Nagasaka","sequence":"additional","affiliation":[{"name":"Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9213-0325","authenticated-orcid":false,"given":"Karen L.","family":"Reckamp","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiama N.","family":"Waqar","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8691-0387","authenticated-orcid":true,"given":"Jessica R.","family":"Bauman","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6070-2413","authenticated-orcid":true,"given":"Alison M.","family":"Schram","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-3811","authenticated-orcid":true,"given":"Shirish M.","family":"Gadgeel","sequence":"additional","affiliation":[{"name":"Henry Ford Cancer Institute\/Henry Ford Health System, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8425-1223","authenticated-orcid":true,"given":"Patrick C.","family":"Ma","sequence":"additional","affiliation":[{"name":"Penn State Cancer Institute, Penn State University, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartik","family":"Konduri","sequence":"additional","affiliation":[{"name":"Baylor Charles A. Sammons Cancer Center, Texas Oncology PA, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2479-2271","authenticated-orcid":true,"given":"Danny","family":"Nguyen","sequence":"additional","affiliation":[{"name":"City of Hope, Huntington Beach, CA"},{"name":"City of Hope, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7747-0948","authenticated-orcid":true,"given":"Jamal","family":"Misleh","sequence":"additional","affiliation":[{"name":"Medical Oncology Hematology Consultants, Newark, DE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-7285","authenticated-orcid":true,"given":"Jonathan","family":"Bleeker","sequence":"additional","affiliation":[{"name":"Sanford USD Medical Center, Sioux Falls, SD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2744-0973","authenticated-orcid":true,"given":"Matthias","family":"Weiss","sequence":"additional","affiliation":[{"name":"ThedaCare Cancer Center, Appleton, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-6709","authenticated-orcid":true,"given":"Subotheni","family":"Thavaneswaran","sequence":"additional","affiliation":[{"name":"The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric B.","family":"Haura","sequence":"additional","affiliation":[{"name":"H. 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