{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:22:28Z","timestamp":1792790548791,"version":"4.5.0"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"30","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Presently, to our knowledge, there are no approved targeted therapies for neuregulin 1 gene fusion\u2013positive (\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      +) cholangiocarcinoma. Zenocutuzumab, a HER2 \u00d7 HER3 bispecific antibody, is approved for previously treated, advanced\/metastatic\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      + non\u2013small cell lung cancer and pancreatic adenocarcinoma. Here, we report results for 22 patients with\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      + cholangiocarcinoma in the eNRGy trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      eNRGy is a single-arm, phase II study of zenocutuzumab in advanced\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      + solid tumors. Patients were age 18 years and older and previously treated with or unsuitable for standard therapy. Zenocutuzumab 750 mg was administered intravenously once every 2 weeks. The primary end point was investigator-assessed overall response rate (ORR; RECIST v1.1). Secondary end points included duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS), and safety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      As of July 31, 2025, 22 patients (median age 57.5 years) with advanced\n                      <jats:italic toggle=\"yes\">NRG1<\/jats:italic>\n                      + cholangiocarcinoma were enrolled and had received a median of 1.0 (range, 0-6) prior therapies. In the 18 patients with tumor subtype data available, all had intrahepatic cholangiocarcinoma. Three patients did not meet the protocol-defined criteria for inclusion in the efficacy analysis. Seven of 19 patients achieved a response, resulting in an ORR of 36.8% (95% CI, 16.3 to 61.6). The median DOR was 7.4 months and the median time to response was 1.9 months. The CBR was 57.9% (95% CI, 33.5 to 79.7). Median PFS was 9.2 months (95% CI, 3.9 to 11.1). Most treatment-related adverse events (TRAEs) were grade 1 and 2, and the most common were diarrhea (27.3%), fatigue (18.2%), and nausea (13.6%). One patient had a grade 3 TRAE of anemia. No patients discontinued treatment due to an AE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Zenocutuzumab demonstrated clinically meaningful and durable antitumor activity with a favorable safety profile in patients with advanced\n                      <jats:italic toggle=\"yes\">NRG1+<\/jats:italic>\n                      cholangiocarcinoma.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-03128","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:00:09Z","timestamp":1782936009000},"page":"2908-2918","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and Tolerability of Zenocutuzumab in Advanced\n                    <i>NRG1<\/i>\n                    Fusion\u2013Positive Cholangiocarcinoma: Results From the eNRGy Phase II Trial"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct02912949","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-3951","authenticated-orcid":false,"given":"James M.","family":"Cleary","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-101X","authenticated-orcid":false,"given":"Christoph","family":"Springfeld","sequence":"additional","affiliation":[{"name":"Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-599X","authenticated-orcid":false,"given":"Dirk","family":"Arnold","sequence":"additional","affiliation":[{"name":"Asklepios Klinik Altona, Hamburg, 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Universit\u00e0 degli Studi di Milano, Milan, Italy"},{"name":"Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Opdam","sequence":"additional","affiliation":[{"name":"Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0163-7543","authenticated-orcid":false,"given":"Yu","family":"Sunakawa","sequence":"additional","affiliation":[{"name":"St Marianna University Hospital, Kawasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3857-1688","authenticated-orcid":false,"given":"Philippe A.","family":"Cassier","sequence":"additional","affiliation":[{"name":"Centre L\u00e9on B\u00e9rard, Lyon, 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