BeOne starts another front-line sonrotoclax fight
The new phase 3 trial, in first-line CLL, is expected to begin in January 2026.
The new phase 3 trial, in first-line CLL, is expected to begin in January 2026.
BeOne Medicines is continuing to expand its pivotal clinical programme for the combination of Brukinsa and the BCL-2 inhibitor sonrotoclax, as it tries to position the doublet as “the best oral combo fixed-duration regimen in treatment-naive CLL”.
The company has recently posted a new pivotal study on clinicaltrials.gov evaluating the Brukinsa-sonrotoclax combination in the front-line setting. As with the phase 3 trial BGB-11417-301, initiated in 2023, the new study targets previously untreated CLL, but has a different comparator. While 301 has Gazyva and Venclexta as the control, the new study, BGB-11417-304, will use Calquence plus Venclexta, with the same primary endpoints, MRD rate and progression-free survival.
The new trial might have been spurred by the changing CLL space, which has seen BTK inhibitors like Imbruvica, Brukinsa and Calquence playing an increasingly active role. Current NCCN guidelines emphasise these drugs as key options for first-line CLL, although Gazyva is also still recommended, in combo with Venclexta as well as with Calquence and Imbruvica.
ASH data
The new listing comes not long after BeOne presented updated results from the phase 1 BGB-11417-101 study, from a cohort of first-line CLL patients, at ASH.
Among 135 efficacy-evaluable patients treated with sonrotoclax plus Brukinsa, 100% responded, with half of the subjects in the 320mg group achieving complete response or complete response with incomplete marrow recovery. With nearly 31 months of follow-up, no progression events were observed in the 320mg cohort. No cases of clinical or laboratory tumour lysis syndrome were reported, and no treatment-emergent adverse events resulted in death.
On a cross-trial basis these data look better than those from the Amplify trial of Calquence plus Venclexta, where ORR was 93%, and the three-year PFS rate was 77%.
The sonrotoclax/Brukinsa combo will need to show a similar benefit in the upcoming 304 study, which is slated to start in January 2026.
Selected pivotal sonrotoclax trials
| Trial | Indication | Design | Status |
|---|---|---|---|
| BGB-11417-201 | r/r MCL (post BTKi & anti-CD20 Mab) | Phase 1/2 monotherapy | Accepted for FDA review Nov 2025, with priority review |
| Celestial-TNCLL (301) | 1st-line CLL | Phase 3, + Brukinsa, vs Gazyva + Venclexta | MRD data expected in 2026, with potential to support conditional approval |
| Celestial-203 | Waldenström’s macroglobulinemia | Phase 2, monotherapy (r/r) & Brukinsa combo (1st-line) | Enrolment completed Nov 2025 |
| Celestial-RRMCL | r/r MCL (post anti-CD20 MAb) | Phase 3, + Brukinsa, vs Brukinsa | Confirmatory study; expected completion Mar 2029 |
| Celestial-RRCLL | r/r CLL | Phase 3, + Gazyva/Rituxan, vs Venclexta + Rituxan | Expected completion Dec 2029 |
| Celestial-TNCLL (304) | 1st-line CLL | Phase 3, + Brukinsa, vs Calquence + Venclexta | MRD data could be reported in 2029 |
Source: OncologyPipeline.
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