A Phase 3, Randomized Study to Compare Nemtabrutinib Versus Comparator (Investigator’s Choice of Ibrutinib or Acalabrutinib) in Participants With Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BELLWAVE-011)

Research summary

This is a randomized, active-controlled, parallel-group, multi-site, open-label study of nemtabrutinib in participants with CLL/SLL who have not received any prior therapy. After providing documented informed consent, suitable candidates will be screened to assess whether they meet all study eligibility criteria. The study will be conducted in conformance with GCP. Approximately 1200 eligible participants will be enrolled and randomly assigned in a 1:1 ratio to 1 of the 2 treatment groups: • Experimental Group – nemtabrutinib • Comparator Group – investigator’s choice of ibrutinib or acalabrutinib The investigator must select and record the choice of comparator treatment (ibrutinib or acalabrutinib) in the IRT and confirm before randomization. Once randomized to the comparator group and treatment is initiated, the comparator treatment (ibrutinib or acalabrutinib) cannot be changed. Participants will also not be allowed to crossover between the nemtabrutinib group and comparator group. Randomization will be stratified by a) TP53 aberration (yes vs no); b) clinical stage (Rai low/intermediate for CLL and Lugano I/II for SLL, vs Rai high for CLL and Lugano III/IV for SLL); c) investigator’s intended choice of comparator: ibrutinib vs acalabrutinib (as determined before randomization); and d) region (US/Canada vs Europe vs Rest of world). Approximately 5% of enrolled participants are expected to have SLL. The first primary endpoint of the study is OR, defined as having CR, CRi, nPR, or PR per iwCLL criteria 2018 as assessed by BICR. The second primary endpoint of the study is PFS, defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first, per iwCLL criteria 2018 as assessed by BICR. Secondary endpoints include OS, DOR, and safety. Tertiary/exploratory endpoints include undetectable MRD, OR including PRL, PFS2, incidence of known molecular resistance development, time to the first presence of molecular resistance, molecular determinants of response or resistance to treatments, ePROs, and PK. Treatment in both groups will continue until unacceptable toxicity, verified disease progression, or another discontinuation criterion is met. Participants should continue treatment until disease progression is centrally verified (disease progression based on imaging results) or verified by Sponsor (disease progression based on non-imaging assessments).

Principal Investigator

Dr Toby Eyre

Contact us

Email: Latephasehaematology@ouh.nhs.uk

IRAS number

1008561