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# Jaypirca Combination Cuts Progression Risk by 45% in CLL Trial: Lilly
- URL: https://www.fdaweb.com/jaypirca-combination-cuts-progression-risk-by-45-in-cll-trial-lilly/
- Published: 2026-06-15T12:00:00.000Z
- Updated: 2026-09-14T13:41:10.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5161307

Eli Lilly is reporting positive Phase 3 results for its BTK inhibitor Jaypirca (pirtobrutinib) in combination with venetoclax and rituximab, showing a significant progression-free survival benefit in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The BRUIN CLL-322 trial met its primary endpoint, demonstrating that adding Jaypirca to a time-limited regimen of venetoclax and rituximab reduced the risk of disease progression or death by 45% compared with venetoclax and rituximab alone.

Lilly said the study is the first Phase 3 trial in CLL to demonstrate superiority over a venetoclax-containing control arm.

The global study enrolled 639 patients with relapsed or refractory CLL/SLL, nearly 80% of whom had previously received a covalent BTK inhibitor, reflecting current treatment patterns. Patients were randomized to receive either pirtobrutinib plus venetoclax and rituximab or venetoclax and rituximab alone.

After a median follow-up of 27.3 months, median progression-free survival had not yet been reached in the pirtobrutinib arm, compared with 39.7 months in the control group, Lilly says. The benefit was observed across multiple patient subgroups, including those previously treated with covalent BTK inhibitors and patients with high-risk disease features such as TP53 mutations, 17p deletions and unmutated IGHV.

In an exploratory analysis of second-line patients whose disease progressed after first-line covalent BTK inhibitor therapy, the pirtobrutinib regimen reduced the risk of progression or death by 68%, with median progression-free survival not reached compared with 28.3 months for the control arm, according to the company.

Overall survival data remain immature, although a secondary endpoint measuring time to next treatment also favored the pirtobrutinib combination, with a 50% reduction in the risk of requiring subsequent therapy, it says.

Jaypirca is currently approved for treating adults with relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor and for certain patients with relapsed or refractory mantle cell lymphoma. Lilly said it plans to submit the BRUIN CLL-322 data to global regulators to support a label expansion.