Eli Lilly and Company announced positive topline results from the Phase 3 BRUIN CLL-322 trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, plus venetoclax and rituximab versus venetoclax and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Treatment in both study arms was administered for up to two years, after which patients do not take any CLL therapy until their disease progresses.
The study met its primary endpoint, demonstrating that the addition of pirtobrutinib to venetoclax plus rituximab led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS), as assessed by an independent review committee (IRC). Results were consistent across clinically relevant subgroups and regardless of whether patients were previously treated with a covalent BTK inhibitor.
Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis, but was trending in favor of the pirtobrutinib combination regimen. The overall safety profile of this regimen was consistent with the known safety profile of each medicine. Rates of adverse events were similar across the study arms, with low rates of treatment regimen discontinuations, also similar between arms.
Detailed results will be presented at a medical congress and submitted to a peer-reviewed journal. Lilly intends to submit these results to regulators later this year for a label expansion.
"BRUIN CLL-322 was an ambitious trial, building on an effective regimen, and these results outperformed our expectations," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "Modern CLL treatment regimens provide such durable disease control that the vast majority of patients see their entire disease course managed by only one or two lines of therapy. For doctors and patients who prefer a time-limited approach, these BRUIN CLL-322 data demonstrate that the addition of Jaypirca could further extend the duration of benefit in second line CLL. Together with the other Phase 3 data recently published from the BRUIN clinical program, these data reinforce the potential role that pirtobrutinib may have, whether as a time-limited combination as a second line treatment or as a continuously dosed monotherapy in either line of therapy. We look forward to sharing the detailed data later this year and pursuing regulatory approvals to enable broad access."
These data build on the previously reported positive results from the BRUIN Phase 1/2 trial, the Phase 3 BRUIN CLL-321 trial, the first randomized, controlled study ever conducted in an exclusively post-covalent BTK inhibitor population, the Phase 3 BRUIN CLL-314 trial, the first-ever head-to-head Phase 3 trial versus ibrutinib in CLL to include treatment-naïve patients, and the BRUIN CLL-313 trial, the first prospective, randomized Phase 3 study to examine the efficacy and safety of a non-covalent BTK inhibitor exclusively in patients with treatment-naïve CLL.
Jaypirca (pirtobrutinib) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.
