Nemtabrutinib — Investigational Agent
BTK Inhibitor · Phase 2 · Merck Sharp & Dohme (MSD)
Mechanism of Action
Non-covalent (reversible) BTK inhibitor with a dual mechanism: it inhibits BTK (including the C481S resistance mutant) and additionally suppresses ERK signaling, a parallel survival pathway that can sustain B-cell malignancy growth even in the presence of BTK inhibition. This dual targeting strategy aims to overcome the polyclonal resistance that limits covalent BTKi, where tumor cells can bypass BTK through alternative signaling pathways.
Investigational Indications
- Relapsed/refractory chronic lymphocytic leukemia / SLL — including patients previously treated with covalent BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib)
- Relapsed/refractory mantle cell lymphoma
- Relapsed/refractory diffuse large B-cell lymphoma
- Waldenström's macroglobulinemia
- Marginal zone lymphoma