A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Summary

The purpose of this study is to compare the efficacy and safety of fixed duration pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with CLL/SLL who have been previously treated with at least one prior line of therapy. Participation could last up to five years.

Timeline

Start

2021-09-20

Primary completion

2026-10

Completion

2027-10

Outcome

Met primary endpoint

paper PVR showed a significant improvement in IRC-assessed progression-free survival compared with VR (hazard ratio 0·547 [95% CI 0·400-0·748]; p=0·0001). PMID 42425121 ↗

release “BRUIN CLL-322 is the first Phase 3 study to demonstrate superiority over a venetoclax-containing control arm in CLL” lilly.com ↗

release “The study met its primary endpoint of independent review committee (IRC)-assessed progression-free survival (PFS)” lilly.com ↗

Publications

• Davids MS, Eyre TA, Woyach JA, Roeker LE, Ferrajoli A, Wang Y, Tam CS, Jurczak W, Zinzani PL, Simkovic M, Li JY, Bosch F, Roos-Weil D, Cramer P, Osterborg A, Islam P, Jacobs R, Skarbnik A, Bhat SA, Kang S, Chen M, Nguyen B, McNeely SC, Chung KL, Oliveira JM, Ito R, Ghia P, Wierda WG. Fixed-duration pirtobrutinib plus venetoclax-rituximab versus venetoclax-rituximab for patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (BRUIN CLL-322): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet. 2026 Jul 9:S0140-6736(26)01204-3. doi: 10.1016/S0140-6736(26)01204-3. Online ahead of print.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Pirtobrutinib	Small molecule	—	Oral
Background	Rituximab	Monoclonal antibody	—	Intravenous
Background	Venetoclax	Small molecule	—	Oral

Indications