{"entity":{"id":"nemtabrutinib","kind":"drug","name":"Nemtabrutinib","aka":[],"tldr":"Nemtabrutinib is Merck's reversible BTK blocker, active against the C481S escape mutation, being tested against ibrutinib and acalabrutinib in first-line CLL.","summary":"BELLWAVE-001 (phase 1/2): ORR 53% (including partial response with lymphocytosis) at the 65 mg dose in relapsed CLL/SLL. Phase 3 BELLWAVE-011 (vs ibrutinib or acalabrutinib, untreated CLL) and BELLWAVE-008 (vs chemoimmunotherapy) are recruiting. Also inhibits other kinases (ERK pathway), which may add activity in Richter transformation.","status":"phase-3","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT06136559 (BELLWAVE-011)","url":"https://clinicaltrials.gov/study/NCT06136559"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["btk"],"drugs":[],"companies":["merck"],"institutions":[],"pathways":[],"terms":[],"trials":["bellwave-011","nct03162536","nct05458297","nct04728893","nct05947851","nct05624554"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"MK-1026, ARQ-531","modality":"Small-molecule non-covalent BTK inhibitor","mechanism":"Reversible ATP-competitive inhibitor of wild-type and C481S BTK, with off-target activity on ERK-pathway kinases.","approvals":[],"mechanismSteps":["Binds the BTK ATP pocket reversibly, unaffected by C481S","BCR signalling and downstream ERK signalling are blocked","Once-daily 65 mg dosing"],"dosing":{"route":"Oral","schedule":"65 mg once daily (RP2D)","monitoring":"Dysgeusia, neutropenia, hypertension, infections"},"toxicity":[{"event":"Dysgeusia","anyGradePct":21,"source":"https://www.onclive.com/view/nemtabrutinib-generates-responses-displays-manageable-safety-in-cll-sll"},{"event":"Neutropenia","grade3PlusPct":17},{"event":"Hypertension","anyGradePct":15}],"access":[],"regulatoryEvents":[]},"route":"/drugs/nemtabrutinib/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"cll-relapsed","kind":"cancer","name":"Relapsed or refractory chronic lymphocytic leukaemia","route":"/cancers/cll-relapsed/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"trial":[{"id":"nct03162536","kind":"trial","name":"A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)","route":"/trials/nct03162536/"},{"id":"nct05947851","kind":"trial","name":"A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).","route":"/trials/nct05947851/"},{"id":"nct05624554","kind":"trial","name":"A Study of Nemtabrutinib vs Chemoimmunotherapy for Participants With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without TP53 Aberrations (MK-1026-008, BELLWAVE-008)","route":"/trials/nct05624554/"},{"id":"nct05458297","kind":"trial","name":"A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-","route":"/trials/nct05458297/"},{"id":"bellwave-011","kind":"trial","name":"BELLWAVE-011","route":"/trials/bellwave-011/"},{"id":"nct04728893","kind":"trial","name":"Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)","route":"/trials/nct04728893/"}]}}