SAFETY AND ANTITUMOR ACTIVITY OF NEMTABRUTINIB PLUS VENETOCLAX IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA: PART 1 OF THE PHASE 3 BELLWAVE-010 STUDY

@article{ghia2026safety,
  title = {{SAFETY AND ANTITUMOR ACTIVITY OF NEMTABRUTINIB PLUS VENETOCLAX IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA: PART 1 OF THE PHASE 3 BELLWAVE-010 STUDY}},
  author = {Paolo GHIA and Mauricio CHANDIA CABAS and Vernon Johan LOUW and Carmen MARTINEZ CHAMORRO and Gonzalo GARATE and Valeria BUCCHERI and Raimundo GAZITUA PEPPER and Alejandro BERKOVITS and Michael CASS and Eva GONZALEZ BARCA and Jose SANDOVAL-SUS and Muhit OZCAN and Sven Erik OJAVEE and Ima PAYDAR and Mohammed Z.H. FAROOQUI and Ohad BENJAMINI},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107470},
  url = {https://doi.org/10.1016/j.htct.2026.107470},
  note = {CC BY},
}

TY  - JOUR
TI  - SAFETY AND ANTITUMOR ACTIVITY OF NEMTABRUTINIB PLUS VENETOCLAX IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA: PART 1 OF THE PHASE 3 BELLWAVE-010 STUDY
AU  - Paolo GHIA
AU  - Mauricio CHANDIA CABAS
AU  - Vernon Johan LOUW
AU  - Carmen MARTINEZ CHAMORRO
AU  - Gonzalo GARATE
AU  - Valeria BUCCHERI
AU  - Raimundo GAZITUA PEPPER
AU  - Alejandro BERKOVITS
AU  - Michael CASS
AU  - Eva GONZALEZ BARCA
AU  - Jose SANDOVAL-SUS
AU  - Muhit OZCAN
AU  - Sven Erik OJAVEE
AU  - Ima PAYDAR
AU  - Mohammed Z.H. FAROOQUI
AU  - Ohad BENJAMINI
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107470
UR  - https://doi.org/10.1016/j.htct.2026.107470
AB  - Background: Venetoclax plus rituximab (VR) is a standard-of-care therapy for relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). However, the need for more effective treatments remains unmet. Nemtabrutinib is a reversible Bruton tyrosine kinase inhibitor that showed durable antitumor activity in participants with CLL/SLL in the phase 1/2 BELLWAVE-001 study. The open-label, randomized, phase 3 BELLWAVE-010 study (NCT05947851) is evaluating the safety and efficacy of nemtabrutinib plus venetoclax versus VR in R/R CLL/SLL. Herein, we present the results from part 1, the nonrandomized dose-escalation and confirmation phase of the study. Aim: To evaluate the safety and efficacy of nemtabrutinib plus venetoclax. Materials and methods: Participants aged ≥ 18 years with CLL/SLL R/R to ≥ 1 prior therapy per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria and an ECOG PS score of 0–2 received nemtabrutinib 45 or 65 mg orally once daily for 4 weeks, followed by nemtabrutinib + venetoclax (20–400 mg orally once daily escalated over 28 days). Primary end points were safety and tolerability, including dose-limiting toxicities (DLTs), and establishment of the recommended dose of nemtabrutinib plus venetoclax. Efficacy end points for part 1 were ORR and DOR per iwCLL 2018 criteria by BICR. Results: As of the data cutoff date (April 9, 2025), 31 participants were enrolled in the DLT-evaluable population; 15 received nemtabrutinib 45 mg plus venetoclax and 16 received nemtabrutinib 65 mg plus venetoclax. Median study follow-up was 10.3 months (range, 1.2–19.4). Median age was 70 years (range, 39–89); 22 participants (71%) were male, 5 (16%) had received ≥ 3 prior lines of therapy, and 3 (10%) had an ECOG PS score of 2. Among the DLT-evaluable population, 2 (6%) discontinued treatment due to an AE. DLTs were reported in 2 participants with nemtabrutinib 65 mg (both pneumonia: one grade 3 [resolved] and one grade 5). Any-grade TEAEs were reported in all participants (100%) in both arms. Grade 3–5 TEAEs occurred in 11 participants (73%) in the nemtabrutinib 45-mg arm and 12 participants (75%) in the nemtabrutinib 65-mg arm. One death due to a TEAE occurred in the nemtabrutinib 65-mg arm (pneumonia); none occurred in the nemtabrutinib 45-mg arm. The most common TEAEs of any grade (incidence ≥ 40% in either arm) were neutropenia (53% and 50%), diarrhea (40% and 19%), and thrombocytopenia (40% and 44%). The ORR was 100% (95% CI, 78%–100%; CR, 13%; PR, 87%) in the nemtabrutinib 45-mg arm and 88% (95% CI, 62%–98%; CR, 13%; PR, 75%) in the nemtabrutinib 65-mg arm. Median DOR was not reached in either arm. The maximum percent change from baseline of target lesions sum of product of diameters was > 50% in 93% of participants in both arms. Discussion: Although efficacy outcomes are still maturing due to short follow-up time, these initial results show promising antitumor activity for nemtabrutinib 45 mg plus venetoclax and a manageable safety profile. Conclusions: These findings from part 1 of the ongoing phase 3 BELLWAVE-010 study support the ongoing evaluation of nemtabrutinib plus venetoclax in participants with R/R CLL/SLL.
SN  - 2531-1379
SN  - 2531-1387
ER  -