{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:58:23Z","timestamp":1789016303866,"version":"build-2803163510"},"reference-count":25,"publisher":"American Association for Cancer Research (AACR)","issue":"1","funder":[{"name":"Merck"}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Nemtabrutinib is an orally bioavailable, reversible inhibitor of Bruton tyrosine kinase (BTK) and C481S mutant BTK. We evaluated the safety, pharmacology, and antitumor activity of nemtabrutinib in relapsed\/refractory hematologic malignancies. Forty-eight patients with chronic lymphocytic leukemia (CLL), B-cell non\u2013Hodgkin lymphoma (NHL), or Waldenstr\u00f6m macroglobulinemia (WM), relapsed\/refractory after\u00a0\u22652 prior therapies were enrolled in the open-label, single-arm, phase I MK-1026-001 study (NCT03162536) to receive nemtabrutinib 5 to 75 mg once daily in 28-day cycles. Dose finding progressed using a 3\u00a0+\u00a03 dose escalation design. Primary endpoints were safety and the recommended phase II dose (RP2D). Among 47 treated patients, 29 had CLL, 17 had NHL, and 1 had WM. Grade\u00a0\u22653 treatment-emergent adverse events occurred in 37 (89%), most commonly neutropenia (11; 23.4%), febrile neutropenia (7; 14.9%), and pneumonia (7; 14.9%). The RP2D was 65 mg daily. An overall response rate of 75% was observed in patients with CLL at 65 mg daily.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>This first-in-human phase I study demonstrates the safety and preliminary efficacy of nemtabrutinib in patients with relapsed\/refractory B-cell malignancies. These data support further exploration of nemtabrutinib in larger clinical studies.<\/jats:p>\n                    <jats:p>This article is featured in Selected Articles from This Issue, p. 5<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-23-0670","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T09:07:16Z","timestamp":1699261636000},"page":"66-75","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["First-in-Human Study of the Reversible BTK Inhibitor Nemtabrutinib in Patients with Relapsed\/Refractory Chronic Lymphocytic Leukemia and B-Cell Non\u2013Hodgkin Lymphoma"],"prefix":"10.1158","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3403-9144","authenticated-orcid":false,"given":"Jennifer A.","family":"Woyach","sequence":"first","affiliation":[{"name":"1Ohio State University, Columbus, 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