BELLWAVE-010: A phase 3 study of nemtabrutinib plus venetoclax versus venetoclax plus rituximab (VR) in previously treated patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Bibliographic record
Abstract
TPS7089 Background: VR is a standard of care option for pts with CLL/SLL who have relapsed after ≥1 line of prior therapy. However, there is an unmet need for more effective treatments. Bruton tyrosine kinase (BTK) plays an important role in the pathogenesis of CLL. Nemtabrutinib is a BTK inhibitor that targets both wild type and C481-mutant forms of BTK. In the ongoing BELLWAVE-001 study, nemtabrutinib demonstrated manageable safety and durable antitumor activity in pts with R/R CLL/SLL with and without C481 mutations. The randomized, open-label, phase 3 BELLWAVE-010 study (NCT05947851) is designed to evaluate the efficacy and safety of nemtabrutinib + venetoclax versus VR as second-line or later treatment for pts with R/R CLL/SLL. Methods: Eligible pts are aged ≥18 years with active R/R CLL/SLL after ≥1 prior therapy per iwCLL 2018 criteria and an ECOG PS of 0-2. Approximately 720 pts will be enrolled in 2 parts. Part 1 is an open-label, nonrandomized dose escalation and confirmation phase to evaluate safety and determine the optimal dose of nemtabrutinib + venetoclax. Part 1 will enroll 30 pts to establish the dose of nemtabrutinib using a modified toxicity probability interval design. Pts will receive nemtabrutinib at 2 dose levels (45 mg PO QD starting dose, escalating to 65 mg PO QD) for 28 days, followed by nemtabrutinib + venetoclax (20-400 mg PO QD ramp up over 4 weeks). Part 2 is an open-label, parallel-group, randomized phase comparing the efficacy and safety of nemtabrutinib + venetoclax with VR. In part 2, approximately 690 pts will be randomly assigned 1:1 to receive either nemtabrutinib at the recommended dose for 28 days followed by the nemtabrutinib + venetoclax or venetoclax + rituximab (or rituximab biosimilar; 375 mg/m2 at week 6, followed by 500 mg/m2 every 4 weeks starting at week 10 until week 26 [total 6 doses]). Study treatment will continue for approximately 2 years or until unacceptable toxicity, disease progression, or other discontinuation criteria are met. Randomization will be stratified by BTK-C481 mutation status (detected vs not detected), geographic region (US/Canada vs Europe vs rest of world) and risk (high risk [del(17p) and/or TP53-mutated and/or IGHV-unmutated] vs low risk [absence of high-risk factors]). The primary end point for part 2 is progression-free survival by blinded independent central review (BICR) per iwCLL 2018 criteria. Secondary end points for part 2 are undetectable minimal residual disease in bone marrow at month 14 by central laboratory assessment, objective response rate (ORR), and duration of response by BICR per iwCLL 2018 criteria, overall survival, and safety. Exploratory end points are ORR including partial response with lymphocytosis, pharmacokinetics, and health-related quality of life. Recruitment is ongoing. Clinical trial information: NCT05947851 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.012 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".