{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:13:20Z","timestamp":1793945600800,"version":"4.8.0"},"reference-count":16,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Pirtobrutinib, a highly selective, noncovalent Bruton tyrosine kinase inhibitor (BTKi), has shown efficacy and safety in patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL) who received prior covalent BTKi. We report results, to our knowledge, from the first randomized head-to-head comparison of pirtobrutinib versus ibrutinib in BTKi-na\u00efve CLL\/SLL in both treatment-na\u00efve (TN) patients and patients with relapsed\/refractory (R\/R) disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      Patients (N = 662) were randomly assigned 1:1 to receive pirtobrutinib or ibrutinib. All patients were BTKi-na\u00efve. Primary end points were overall response rate (ORR) by independent review committee (IRC) among all randomly assigned patients (intention to treat [ITT]) and in patients with R\n                      <jats:bold>\/<\/jats:bold>\n                      R disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The study met its primary end points, demonstrating statistically significant noninferiority (NI) of IRC-ORR for pirtobrutinib versus ibrutinib in both the ITT (87.0% [95% CI, 82.9 to 90.4]\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      78.5% [95% CI, 73.7 to 82.9]; ORR ratio = 1.11 [95% CI, 1.03 to 1.19]; two-sided\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001) and R\/R populations (n = 437; 84.0% [95% CI, 78.5 to 88.6]\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      74.8% [95% CI, 68.5 to 80.4]; ORR ratio = 1.12 [95% CI, 1.02 to 1.24]; two-sided\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). In TN patients (n = 225), IRC-ORR was 92.9% (95% CI, 86.4 to 96.9) with pirtobrutinib versus 85.8% (95% CI, 78.0 to 91.7) with ibrutinib. Investigator assessed ORR results were consistent. Investigator-assessed progression-free survival (PFS) favored pirtobrutinib in the ITT (hazard ratio [HR], 0.57 [95% CI, 0.39 to 0.83]), R\/R (HR, 0.73 [95% CI, 0.47 to 1.13]), and TN (HR, 0.24 [95% CI, 0.10 to 0.59]) populations. Cardiac adverse event rates of atrial fibrillation\/flutter and hypertension were lower with pirtobrutinib.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Pirtobrutinib demonstrated NI of ORR versus ibrutinib, with a favorable early PFS trend, particularly in TN patients, and a favorable safety profile including low rates of atrial fibrillation and hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02477","type":"journal-article","created":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T22:39:05Z","timestamp":1765147145000},"page":"476-485","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Pirtobrutinib Versus Ibrutinib in Treatment-Na\u00efve and Relapsed\/Refractory Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct05254743","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3403-9144","authenticated-orcid":false,"given":"Jennifer A.","family":"Woyach","sequence":"first","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lugui","family":"Qiu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Grosicki","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention, Medical University of Silesia, Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-3535","authenticated-orcid":false,"given":"Tomasz","family":"Wrobel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cellular Therapies and Internal Medicine, Medical University of Wroclaw, Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5224-1979","authenticated-orcid":false,"given":"Marcelo","family":"Capra","sequence":"additional","affiliation":[{"name":"Centro Integrado de Hematologia e Oncologia, Hospital M\u00e3e de Deus, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-7837","authenticated-orcid":false,"given":"Jaroslaw","family":"Czyz","sequence":"additional","affiliation":[{"name":"Departament of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Torun, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-812X","authenticated-orcid":false,"given":"Shuhua","family":"Yi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Tianjin, China"},{"name":"Tianjin Institutes of Health Science, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0578-126X","authenticated-orcid":false,"given":"Ki-Seong","family":"Eom","sequence":"additional","affiliation":[{"name":"Department of Hematology, Catholic Hematology Hospital, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of (South)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4955-3039","authenticated-orcid":false,"given":"Anna","family":"Panovsk\u00e1","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2014Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-8084","authenticated-orcid":false,"given":"Wojciech","family":"Jurczak","sequence":"additional","affiliation":[{"name":"Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-7570","authenticated-orcid":false,"given":"Kamel","family":"Laribi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Centre Hospitalier Le Mans, Le Mans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Jacobasch","sequence":"additional","affiliation":[{"name":"Praxis of Haematology and Oncology, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2728-6788","authenticated-orcid":false,"given":"Ross","family":"Baker","sequence":"additional","affiliation":[{"name":"Perth Blood Institute, Perth, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richy","family":"Agajanian","sequence":"additional","affiliation":[{"name":"The Oncology Institute of Hope and Innovation, Whittier, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Berkovits","sequence":"additional","affiliation":[{"name":"Inmunocel, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhit","family":"\u00d6zcan","sequence":"additional","affiliation":[{"name":"Ankara University, School of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Lepretre","sequence":"additional","affiliation":[{"name":"Centre de Lutte Contre le Cancer\u2014Centre Henri Becquerel Normandie Rouen, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine C.","family":"Coombs","sequence":"additional","affiliation":[{"name":"University of California Irvine, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4046-9922","authenticated-orcid":false,"given":"Paula","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German Chronic Lymphocytic Leukemia Study Group, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0549-5877","authenticated-orcid":false,"given":"Katharine L.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia"},{"name":"Division of Internal Medicine, Medical School, University of Western Australia, Perth, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Hill","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-2387","authenticated-orcid":false,"given":"Katherine","family":"Bao","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Bian","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Ramalho","family":"De Batista Ribeiro","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-8021","authenticated-orcid":false,"given":"Naleen Raj","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching Ching","family":"Leow","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-270X","authenticated-orcid":false,"given":"William G.","family":"Wierda","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_13_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-127674"},{"key":"e_1_3_13_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.2282"},{"key":"e_1_3_13_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400029"},{"key":"e_1_3_13_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01210"},{"key":"e_1_3_13_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211582"},{"key":"e_1_3_13_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30262-2"},{"key":"e_1_3_13_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00293-5"},{"key":"e_1_3_13_9_2","first-page":"62","article-title":"Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor","volume":"142","author":"Gomez EB","year":"2023","unstructured":"Gomez EB, Ebata K, Randeria HS, et al: Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor. Blood 142:62-72, 2023","journal-title":"Blood"},{"key":"e_1_3_13_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2300696"},{"key":"e_1_3_13_11_2","unstructured":"Eli Lilly and Company: Jaypirca [Prescribing Information]. Indianapolis IN Eli Lilly and Company 2024"},{"key":"e_1_3_13_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-00166"},{"key":"e_1_3_13_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-806398"},{"key":"e_1_3_13_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2013.807748"},{"key":"e_1_3_13_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2023.09.002"},{"key":"e_1_3_13_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2020000118"},{"key":"e_1_3_13_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-194748"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-25-02477","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T22:59:34Z","timestamp":1772665174000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-25-02477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,2,20]]}},"alternative-id":["10.1200\/JCO-25-02477"],"URL":"https:\/\/doi.org\/10.1200\/jco-25-02477","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1200\/JCO.25.1209","asserted-by":"subject"}]},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"assertion":[{"value":"2025-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-30","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}