{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:35:20Z","timestamp":1792017320222,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01 CA203628\u201007A1; B. Ogretmen, PI"],"award-info":[{"award-number":["P01 CA203628\u201007A1; B. Ogretmen, PI"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100024219","name":"RedHill Biopharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100024219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Opaganib is a first\u2010in\u2010class oral sphingolipid metabolism inhibitor that inhibits sphingosinekinase 2 (SphK2) and dihydroceramide desaturase (DES) and that has a demonstrated safety and preliminary anti\u2010cancer activity signal in a Phase I study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this phase II trial, patients with metastatic castration\u2010resistant prostate cancer who had disease progression on novel hormonal agents (NHAs) abiraterone or enzalutamide were enrolled and treated with opaganib while continuing their NHA. After safety lead\u2010in cohorts, the trial enrolled cohort 2 (abiraterone + opaganib 500\u2009mg Q 12\u2009h) and cohort 3 (enzalutamide + opaganib 500\u2009mg Q 12\u2009h). The primary efficacy endpoint was the proportion of patients with disease control at Day 113. The postulated disease control rate was 10%. Secondary efficacy endpoints include prostate\u2010specific antigen (PSA) progression\u2010free survival (PSA\u2010PFS) and PSA response rates. The primary safety endpoint was the incidence of adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The disease control rates were 15% (95% CI\u2009=\u20094%\u201335%, 4 of 26 patients) in cohort 2 and 9% (95% CI\u2009=\u20092%\u201324%, 3 of 34 patients) in cohort 3. The median PSA\u2010PFS was 56\u2009days (95% CI\u2009=\u200935\u2013112\u2009days) in cohort 2 and 55\u2009days (95% CI\u2009=\u200935\u201356\u2009days) in cohort 3. The most common AEs of grade 3 or higher were hypertension (8%) and musculoskeletal AEs (8%) in cohort 2 and grade 3 anemia (18%) in cohort 3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The trial did not meet its primary objective of demonstrating 30% disease control at 113\u2009days. However, subjects who experienced a PSA response or stabilization warrant further exploration for biomarkers of response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      number: NCT04207255\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71633","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T03:35:37Z","timestamp":1776224137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phase\n                    <scp>II<\/scp>\n                    Trial of Opaganib Addition in Metastatic Castration\u2010Resistant Prostate Cancer After Disease Progression on Abiraterone or Enzalutamide"],"prefix":"10.1002","volume":"15","author":[{"given":"Jacqueline T.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Hematology and Medical Oncology Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Winship Cancer Institute of Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6385-1329","authenticated-orcid":false,"given":"Bassel","family":"Nazha","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Winship Cancer Institute of Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-3923","authenticated-orcid":false,"given":"Anna C.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent","family":"Armeson","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth G.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Besim","family":"Ogretmen","sequence":"additional","affiliation":[{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikhar","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Brisendine","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Magrath","sequence":"additional","affiliation":[{"name":"Department of Opthalmology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry F.","family":"Plasse","sequence":"additional","affiliation":[{"name":"RedHill Biopharma Ltd  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore Stewart","family":"Gourdin","sequence":"additional","affiliation":[{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Division of Hematology\u2010Oncology, Department of Medicine Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Kucuk","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Winship Cancer Institute of Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lilly","sequence":"additional","affiliation":[{"name":"Hollings Cancer Center Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Division of Hematology\u2010Oncology, Department of Medicine Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040720"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(10)61389\u2010x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911206"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00237\u20103"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107322"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2015.02.025"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/381800a0"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2016.03.001"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502207200"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.Mcr\u201011\u20100336"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201013\u20102732"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.163337"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.11.7.14903"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7914"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.163444"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.Mcr\u201014\u20100626"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.Mct\u201015\u20100279"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000499292"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201016\u20102363"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008\u2010682x.126378"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2015.64.2702"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2018.11.005"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.02.055"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010019\u20105729\u20107"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119115"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)00367\u20101"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(23)00230\u20109"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.5074"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.75.3335"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds091"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g1219"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.21.02810"},{"issue":"2","key":"e_1_2_12_36_1","first-page":"S954","article-title":"1765O \u2010 Interim Results From a Phase I Study of AMG 509 (Xaluritamig), a STEAP1 x CD3 XmAb 2+1 Immune Therapy, in Patients With Metastatic Castration\u2010Resistant Prostate Cancer (mCRPC)","volume":"34","author":"Kelly W.","year":"2023","journal-title":"Annals of Oncology"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.09.2752"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.4_suppl.18"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103625"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010022\u201005056\u20107"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2016.0090"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfo.2022.05.007"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/iae.0000000000002965"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13677"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3928\/23258160\u201020231205\u201002"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2021.3331"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/icb.0000000000000999"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633\u2010021\u201009862\u20108"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242316901"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71633","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.71633","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71633","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:10:33Z","timestamp":1777007433000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.71633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/cam4.71633"],"URL":"https:\/\/doi.org\/10.1002\/cam4.71633","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71633"}}