Abstract
Context: Currently, the majority of patients with chronic lymphocytic leukemia (CLL) who require treatment receive a covalent Bruton's tyrosine kinase inhibitor (BTKi) as their first standard of care targeted therapy. The MURANO study established the time-limited combination of venetoclax plus rituximab (2 years) as a standard of care regimen for patients with relapsed/refractory (R/R) CLL or small lymphocytic lymphoma (SLL). MURANO enrolled very few patients who were previously treated with a covalent BTKi. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that inhibits both wild-type and C481-mutated BTK with equally low nM potency. Objective: Adding fixed-duration pirtobrutinib to the MURANO regimen may allow for deeper remissions and longer disease control and generate a clinically relevant dataset in a population of patients with BTKi-pretreated R/R CLL/SLL. Design: BRUIN CLL-322 is a randomized, open-label, global phase 3 trial comparing fixed duration pirtobrutinib plus venetoclax and rituximab with standard venetoclax and rituximab in patients with R/R CLL/SLL. Approximately 600 patients will be randomized 1:1. Randomization will be stratified by 17p deletion (yes/no) and prior BTKi experience (discontinuation due to progressive disease vs. due to other reasons vs. no prior BTKi exposure). Setting: Global; community hospitals, academic medical centers. Patients: Eligible patients are adults with a diagnosis of CLL/SLL who require therapy per iwCLL 2018 criteria and who received prior therapy that may or may not include a covalent BTKi. Key exclusion criteria include CNS involvement by CLL/SLL, Richter transformation at any time pre-enrollment, history of allogeneic or autologous stem cell transplant or chimeric antigen receptor (CAR) T-cell therapy within 60 days, and prior therapy with a BCL2 inhibitor or non-covalent BTKi. There will be no exclusion based on the number of lines of prior therapy. Intervention: Fixed-duration pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab. Main Outcome Measures: The primary endpoint is progression-free survival per iwCLL criteria assessed by an independent review committee. Secondary endpoints include overall response rate, overall survival, time to next treatment, event-free survival, safety and tolerability, and patient-reported outcomes. This global study is currently enrolling patients (NCT04965493). Results: This study is a trial in progress. Conclusions: This study is a trial in progress.
Original language | English |
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Article number | CLL-116 |
Pages (from-to) | S267 |
Number of pages | 1 |
Journal | Clinical Lymphoma, Myeloma and Leukemia |
Volume | 22 |
DOIs | |
Publication status | Published - Oct 2022 |
Externally published | Yes |
Event | Society of Hematologic Oncology Annual Meeting 2022 - Houston, United States of America Duration: 28 Sept 2022 → 1 Oct 2022 Conference number: 10th https://www.sciencedirect.com/journal/clinical-lymphoma-myeloma-and-leukemia/vol/22/suppl/S2 |
Keywords
- BCL2i
- BTKi
- chronic lymphocytic leukemia
- CLL
- pirtobrutinib
- Trial-in-Progress
- venetoclax