{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:24:36Z","timestamp":1793118276893,"version":"4.5.0"},"reference-count":47,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"35","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Zelenectide pevedotin (BT8009) is a Bicycle Drug Conjugate comprising a highly selective Nectin-4\u2013targeting Bicycle peptide, linked to monomethyl auristatin E. We report monotherapy dose-escalation results from Duravelo-1 (Phase I\/II; 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\/NCT04561362\">NCT04561362<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Adults with advanced\/metastatic solid tumors associated with Nectin-4 expression received zelenectide pevedotin intravenously at 2.5, 5.0, or 7.5 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      once weekly on a 28-day cycle; or 7.5 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      on days 1 and 8 of a 21-day cycle; or 7.5 or 10.0 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      once every 2 weeks on a 28-day cycle. Primary objectives were to evaluate safety and tolerability; antitumor activity and pharmacokinetic characterization were secondary objectives.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Forty-nine patients, most with urothelial carcinoma (UC; 25 of 49), received three previous lines of therapy (median). Common treatment-related adverse events (TRAEs) included nausea (49% [grade 3\/4 2%]), likely because of a lack of prophylactic antiemetics during the dose-limiting toxicity period, and fatigue (39% [grade 3\/4 6%]). The most common TRAEs of clinical interest were peripheral neuropathy (33% [grade 3\/4 2%]), neutropenia (22% [grade 3\/4 16%]), and skin reactions (22% [grade 3\/4 2%]). The maximum tolerated dose was 7.5 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      once every 2 weeks; the recommended phase 2 doses were 5.0 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      once weekly and 7.5 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      on days 1 and 8 of a 21-day cycle. Across doses (efficacy-evaluable; all tumor types), the objective response rate (ORR) was 24% and the clinical benefit rate (CBR) was 48% (n = 10 of 42; 95% CI, 12.1 to 39.5); the ORR was 38% and the CBR was 57% for patients with UC (n = 8 of 21; 95% CI, 18.1 to 61.6). The median duration of response and the median follow-up for all patients were 11.1 and 7.4 months, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Zelenectide pevedotin monotherapy demonstrated a generally well-tolerated safety profile and preliminary efficacy, particularly in UC, supporting investigation of UC and non-UC populations in the expansion phase.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00559","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T21:00:06Z","timestamp":1762462806000},"page":"3728-3738","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":16,"title":["First-in-Human, Phase I\/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04561362","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0604-7614","authenticated-orcid":true,"given":"Capucine","family":"Baldini","sequence":"first","affiliation":[{"name":"Drug Development Department (DITEP), Gustave Roussy Cancer Campus, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-4022","authenticated-orcid":true,"given":"Loic","family":"Verlingue","sequence":"additional","affiliation":[{"name":"Centre Leon Berard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2053-8639","authenticated-orcid":true,"given":"Vincent","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Drug Development Department (DITEP), Gustave Roussy Cancer Campus, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Doger de Sp\u00e9ville","sequence":"additional","affiliation":[{"name":"START Madrid-FJD and Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Lostes","sequence":"additional","affiliation":[{"name":"Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-5351","authenticated-orcid":true,"given":"Antoine","family":"Italiano","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Institut Bergoni\u00e9, Bordeaux, France"},{"name":"University of Bordeaux, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Cousin","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Institut Bergoni\u00e9, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9165-2191","authenticated-orcid":true,"given":"Gerald S.","family":"Falchook","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute at HealthONE, Denver, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-2756","authenticated-orcid":true,"given":"Andrea","family":"Necchi","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, Milan, Italy"},{"name":"Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Reig Torras","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Clinic, and Translational Genomics and Targeted Therapeutics in Solid Tumors, IDIBAPS, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-9355","authenticated-orcid":true,"given":"Elisa","family":"Fontana","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute UK, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Carter","sequence":"additional","affiliation":[{"name":"The University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-3632","authenticated-orcid":true,"given":"Jordi","family":"Rodon Ahnert","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6225-7555","authenticated-orcid":true,"given":"Jason R.","family":"Brown","sequence":"additional","affiliation":[{"name":"University Hospitals Seidman Cancer Center, Cleveland, OH"},{"name":"Case Western Reserve University, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie R.","family":"DeMars","sequence":"additional","affiliation":[{"name":"Bicycle Therapeutics Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4582-9561","authenticated-orcid":true,"given":"Kate","family":"Josephs","sequence":"additional","affiliation":[{"name":"Bicycle Therapeutics Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Dickson","sequence":"additional","affiliation":[{"name":"Bicycle Therapeutics Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Xu","sequence":"additional","affiliation":[{"name":"Bicycle Therapeutics Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Bader","sequence":"additional","affiliation":[{"name":"Bicycle Therapeutics Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-3027","authenticated-orcid":true,"given":"Carly","family":"Campbell","sequence":"additional","affiliation":[{"name":"Bicycle Therapeutics Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Sharma","sequence":"additional","affiliation":[{"name":"BicycleTx Ltd, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-7418","authenticated-orcid":true,"given":"Meredith","family":"McKean","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_12_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-19-1092"},{"key":"e_1_3_12_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0875"},{"key":"e_1_3_12_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0238"},{"key":"e_1_3_12_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00065"},{"key":"e_1_3_12_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002883"},{"key":"e_1_3_12_7_2","volume-title":"ADCETRIS (brentuximab vedotin) [package insert]","author":"Seattle Genetics, Inc","unstructured":"Seattle Genetics, Inc: ADCETRIS (brentuximab vedotin) [package insert]. U.S. Food and Drug Administration Website. www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/125388_s056s078lbl.pdf"},{"key":"e_1_3_12_8_2","volume-title":"PADCEV (enfortumab vedotin-ejfv) [package insert]","author":"Astellas Pharma US, Inc","unstructured":"Astellas Pharma US, Inc: PADCEV (enfortumab vedotin-ejfv) [package insert]. U.S. Food and Drug Administration Website. www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/761137s007lbl.pdf"},{"key":"e_1_3_12_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1313"},{"key":"e_1_3_12_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000938"},{"key":"e_1_3_12_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0016"},{"key":"e_1_3_12_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-019-0824-z"},{"key":"e_1_3_12_13_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPGXK0FR4MHIHB"},{"key":"e_1_3_12_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-015-0144-7"},{"key":"e_1_3_12_15_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.28299"},{"key":"e_1_3_12_16_2","doi-asserted-by":"publisher","DOI":"10.5603\/FHC.2011.0005"},{"key":"e_1_3_12_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw678"},{"key":"e_1_3_12_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312117"},{"key":"e_1_3_12_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035807"},{"key":"e_1_3_12_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3671"},{"key":"e_1_3_12_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2021-1197"},{"key":"e_1_3_12_22_2","doi-asserted-by":"publisher","DOI":"10.2307\/2531693"},{"key":"e_1_3_12_23_2","unstructured":"Reference deleted"},{"key":"e_1_3_12_24_2","unstructured":"Reference deleted"},{"key":"e_1_3_12_25_2","unstructured":"Reference deleted"},{"key":"e_1_3_12_26_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02044"},{"key":"e_1_3_12_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-5-70"},{"key":"e_1_3_12_28_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6SC00170J"},{"key":"e_1_3_12_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2015.0064"},{"key":"e_1_3_12_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2016.1156829"},{"key":"e_1_3_12_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.21022"},{"key":"e_1_3_12_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.801199"},{"key":"e_1_3_12_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdcr.2022.01.005"},{"key":"e_1_3_12_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2021.115534"},{"key":"e_1_3_12_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107778"},{"key":"e_1_3_12_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2016.10.012"},{"key":"e_1_3_12_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-021-04250-0"},{"key":"e_1_3_12_38_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-015-9790-0"},{"key":"e_1_3_12_39_2","volume-title":"TIVDAK (tisotumab vedotin-tftv) [package insert]","author":"Seagen Inc","unstructured":"Seagen Inc: TIVDAK (tisotumab vedotin-tftv) [package insert]. U.S. Food and Drug Administration Website. www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/761208Orig1s000lbledt.pdf"},{"key":"e_1_3_12_40_2","volume-title":"POLIVY (polatuzumab vedotin-piiq) [package insert]","author":"Genentech","unstructured":"Genentech: POLIVY (polatuzumab vedotin-piiq) [package insert]. U.S. Food and Drug Administration Website. www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761121s008lbl.pdf"},{"key":"e_1_3_12_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.01.002"},{"key":"e_1_3_12_42_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01643"},{"key":"e_1_3_12_43_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.SABCS22-GS1-11"},{"key":"e_1_3_12_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-024-01576-9"},{"key":"e_1_3_12_45_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2021-391"},{"key":"e_1_3_12_46_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01983"},{"key":"e_1_3_12_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1556-0864(25)00291-6"},{"key":"e_1_3_12_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/1557-3265.SABCS24-P4-10-21"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-25-00559","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T23:00:33Z","timestamp":1764975633000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-25-00559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":47,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2025,12,10]]}},"alternative-id":["10.1200\/JCO-25-00559"],"URL":"https:\/\/doi.org\/10.1200\/jco-25-00559","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]},"assertion":[{"value":"2025-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-07","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}