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The randomised trial that confirmed pirtobrutinib works after other BTK inhibitors fail, leading to full approval in December 2025.
BRUIN CLL-321, trial NCT04666038 sponsored by Eli Lilly through Loxo and reported at ASH 2024 and in JCO in 2025, is the randomised trial that confirmed the non-covalent BTK inhibitor pirtobrutinib works after covalent BTK inhibitors fail in relapsed or refractory chronic lymphocytic leukaemia, leading to full approval on 3 December 2025. It randomised 238 patients to pirtobrutinib or investigator's choice of idelalisib-rituximab or bendamustine-rituximab, met its primary progression-free survival endpoint with a longer time to next treatment, while overall survival was not different because of crossover, and the label was broadened to any prior covalent BTK inhibitor. Whether pirtobrutinib belongs in the frontline, which CLL-313 and CLL-314 test, is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
238 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (median)primary | Pirtobrutinib | 119 | 11.2 months | 0.58 | - | link |
| Idelalisib-rituximab or bendamustine-rituximab | 119 | 8.7 months |
Shares Pirtobrutinib, Relapsed or refractory chronic lymphocytic leukaemia, Eli Lilly (incl. Loxo), Chronic lymphocytic leukaemia.
Shares Pirtobrutinib, Relapsed or refractory chronic lymphocytic leukaemia, BTK (Bruton tyrosine kinase), Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall.
Shares Pirtobrutinib, Relapsed or refractory chronic lymphocytic leukaemia, Eli Lilly (incl. Loxo), Chronic lymphocytic leukaemia.
Shares Pirtobrutinib, Relapsed or refractory chronic lymphocytic leukaemia, Chronic lymphocytic leukaemia, Small-molecule kinase inhibitors.
Shares Pirtobrutinib, Eli Lilly (incl. Loxo), Chronic lymphocytic leukaemia, Small-molecule kinase inhibitors.
Shares Jennifer R. Brown, Relapsed or refractory chronic lymphocytic leukaemia, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia.
Shares Pirtobrutinib, Eli Lilly (incl. Loxo), Small-molecule kinase inhibitors.
Shares Pirtobrutinib, Eli Lilly (incl. Loxo), Chronic lymphocytic leukaemia, Small-molecule kinase inhibitors.