Lilly’s Jaypirca (pirtobrutinib) has demonstrated a significant extension in progression-free survival (PFS) when combined with a venetoclax time-limited regimen in patients with previously treated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The BRUIN CLL-322 trial represents the first Phase 3 readout in CLL to outperform a venetoclax-containing control arm, enrolling a patient population predominantly treated with covalent BTK inhibitors, which is highly relevant to current clinical practice. Although overall survival (OS) data is not yet mature, it is trending positively for the pirtobrutinib combination regimen.

The findings from BRUIN CLL-322 are pivotal as they build on previous positive results from multiple Phase 3 studies involving pirtobrutinib in CLL, including the first randomized controlled study conducted exclusively in a post-covalent BTK inhibitor population. The trial involved 639 patients, randomized to receive either pirtobrutinib plus venetoclax and rituximab or the control regimen of venetoclax and rituximab alone. Importantly, the overall safety profile of the combination regimen was consistent with known profiles of the individual agents, with low rates of treatment discontinuations across both arms.

The implications of these results are substantial for the field of hematologic malignancies. The successful demonstration of pirtobrutinib’s efficacy in this context could shift current research paradigms, particularly in the development of combination therapies for CLL. Furthermore, Lilly’s intention to submit these results for regulatory review later this year could expedite the availability of this regimen for clinical use, potentially altering treatment timelines and strategies for patients with relapsed or refractory CLL/SLL.

Source: investor.lilly.com