- BRUIN CLL-322 is a global Phase 3 randomized study (n=639) in relapsed/refractory CLL/SLL comparing pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab alone
- Time-limited (up to 2 years) addition of pirtobrutinib significantly improved progression-free survival across clinically relevant subgroups; overall survival data are immature
- Overall safety rates and treatment discontinuations were similar between arms, and Lilly plans a congress presentation and regulatory submissions later this year
Trial overview
BRUIN CLL-322 is a global, randomized, open-label Phase 3 study (n=639) comparing the non-covalent BTK inhibitor pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab alone; treatment was time-limited to up to two years with no therapy until progression thereafter; primary endpoint was IRC-assessed progression-free survival (PFS).
Efficacy
The trial met its primary endpoint: adding pirtobrutinib produced a statistically significant and clinically meaningful improvement in PFS, with consistent benefit across clinically relevant subgroups and regardless of prior exposure to covalent BTK inhibitors; overall survival was immature but trended favorably.
Safety
The safety profile of the combination was consistent with known effects of the individual agents, with similar rates of adverse events and treatment discontinuations between arms.
Context and next steps
This is the first Phase 3 readout in CLL to utilize and outperform a venetoclax-containing control arm and represents the fourth positive Phase 3 study of pirtobrutinib in CLL; detailed data will be presented at a medical congress and submitted to regulators and a peer-reviewed journal later this year.
