The race to develop the best BTK degrader for patients who have previously received a BTK inhibitor has seen Nurix take another step towards closing the gap on its rival BeOne by revealing its confirmatory study for bexobrutideg, Daybreak CLL-306.
The confirmatory trial is designed to convert a potential accelerated approval, which Nurix hopes to secure through its phase 2 Daybreak-CLL-201 study, into a full approval. However, it comes with some notable changes from the company’s original plans, and these have now been revealed with the posting of the phase 3 study on clinicaltrials.gov.
Daybreak CLL-306 will ultimately be a head-to-head comparison against Jaypirca. This strategy looks like an attempt to mirror what BeOne is already pursuing in the Cadance-304 trial of its BTK degrader BGB-16673.
Back in October, Nurix had floated the possibility of a physician’s choice design pitting bexobrutideg against Jaypirca or combinations of Rituxan plus either Zydelig or bendamustine. But plans were adjusted once Lilly secured full approval for Jaypirca last December based on the Bruin-CLL-321 trial.
Daybreak CLL-306, expected to start in June, will evaluate bexobrutideg in CLL and SLL patients who are relapsed or refractory to prior covalent BTK inhibitors, with progression-free survival as the primary and overall survival as a secondary endpoint.
The question now is whether BTK degraders can accomplish what Jaypirca couldn't in its own confirmatory trial: deliver a meaningful overall survival benefit.
Early data differentiation
But that is still some way off. First comes the accelerated approval decision, where BeOne holds a timing advantage over Nurix, though not necessarily a clinical one.
Through much of last year both companies had been reporting broadly comparable early-stage data. That changed in December, when BeOne said it was advancing 200mg as the go-forward BGB-16673 dose in the Cadance-101 trial, reporting a 94% best overall response rate among 18 patients treated with that dose.
Nurix’s best showing, by comparison, was an 83% response rate in 18 patients treated in a phase 1b bexobrutideg trial. That response rate was achieved at 600mg, which the company maintains is its optimal dose. Where Nurix might have an edge, however, is on safety. Atrial fibrillation was reported in just one bexobrutideg patient, versus three in the BeOne study.
Infections have also surfaced as a point of scrutiny for BeOne: five patient deaths in the BGB-16673 trial were described as “mostly due to infections”, though the company did not classify these as treatment-related. One additional patient discontinued owing to grade 3 aspergillosis, also deemed unrelated to treatment.
Nurix has been quick to seize on this, noting that its bexobrutideg study showed “no systemic fungal infections, or grade 4 infections of any kind”.
Both companies are now awaiting readouts from their respective phase 2 studies, BeOne’s Cadance-101 and Nurix’s Daybreak-CLL-201. BeOne hopes to file for approval in the second half of 2026 if results are favourable, while Nurix expects to report data in 2027.
Meanwhile, Lilly isn't standing still, this week reporting its first positive pivotal results for Jaypirca in combination, with the Bruin-CLL-322 trial meeting its primary endpoint. The addition of Jaypirca to Venclexta plus Rituxan significantly improved progression-free survival versus Venclexta/Rituxan alone in relapsed/refractory CLL and SLL patients.
Selected phase 3 BTK degrader trials in the post-BTK inhibitor setting
| Project | Company | Trial name | Setting | Regimen | Primary endpoint | Status |
|---|
| BGB-16673 | BeOne | Cadance-304 | Post-covalent BTKi CLL/SLL | Monotherapy, vs Jaypirca | PFS | Started Sep 2025; primary completion Apr 2028 |
| Bexobrutideg | Nurix | Daybreak CLL-306 | Post-covalent BTKi CLL/SLL | Monotherapy, vs Jaypirca | PFS | To start Jun 2026 |
