Woyach JA, Stephens DM, Flinn IW, Bhat SA, Savage RE, Chai F, Eathiraj S, Reiff SD, Muhowski EM, Granlund L, Szuszkiewicz L, Wang W, Schwartz B, Ghori R, Farooqui MZH, Byrd JC
Nemtabrutinib is an orally bioavailable, reversible inhibitor of Bruton's Tyrosine Kinase (BTK) and C481S mutant BTK. We evaluated safety, pharmacology, and antitumor activity of nemtabrutinib in relapsed/refractory hematologic malignancies. Forty-eight patients with chronic lymphocytic leukemia (CLL), B-cell non-Hodgkin lymphoma (NHL), or Waldenstrom's macroglobulinemia (WM), relapsed/refractory after ≥2 prior therapies were enrolled in the open-label, single-arm, phase 1 MK-1026-001 study (NCT03162536) to receive nemtabrutinib 5 mg to 75 mg once-daily in 28-day cycles. Dose finding progressed using a 3+3 dose escalation design. Primary endpoints were safety and the recommended phase 2 dose (RP2D). Among 47 treated patients, 29 had CLL, 17 had NHL, and 1 had WM. Grade ≥3 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.