Zanubrutinib plus obinutuzumab receives accelerated U.S. FDA approval for adult patients with R/R FL

On March 7, 2024, it was announced that the U.S. Food and Drug Administration (FDA) had granted accelerated approval to zanubrutinib, a Bruton’s tyrosine kinase inhibitor; plus obinutuzumab, an anti-CD20 monoclonal antibody, for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL) after ≥2 prior lines of systemic therapy. This approval was based on positive response data from the pivotal phase II ROSEWOOD trial (NCT03332017).¹

The ROSEWOOD trial

ROSEWOOD is an ongoing open-label, multicentre, randomized phase II study investigating the efficacy and safety of zanubrutinib plus obinutuzumab (ZO) compared to obinutuzumab monotherapy in 217 adult patients with relapsed/refractory FL.¹

The key outcomes at a median follow-up of 19 months were as follows^1,2:

• Overall response rate of 69% versus 46% in the ZO and obinutuzumab monotherapy arms, respectively (p = 0.0012), as assessed by an independent review committee
• Median duration of response was not reached in the ZO arm and 14 months in the obinutuzumab monotherapy arm; the 18-month duration of response was 69% in the ZO arm
• Treatment was well-tolerated, with a consistent safety profile to previous studies
• Serious adverse reactions were reported in 35% of patients in the ZO arm
• Zanubrutinib discontinuation due to adverse reactions was reported in 17% of patients in the ZO arm

The U.S. FDA has recommended Zanubrutinib at a dose of 160 mg/twice daily, orally, or 320 mg/ once daily, orally, until disease progression or unacceptable toxicity.²

ZO previously received Fast Track designation and Orphan Drug Designation from the U.S. FDA for patients with relapsed/refractory FL, and Health Canada also approved this treatment for the same indication.

Conclusion

Overall, the accelerated approval of zanubrutinib plus obinutuzumab marks an important clinical development, providing patients in the US with the first and only Bruton’s tyrosine kinase inhibitor for the treatment of advanced FL.