Phase II ROSEWOOD Study Shows Doublet Has ‘Meaningful Activity’ in Follicular Lymphoma

Zanubrutinib plus obinutuzumab “demonstrated meaningful activity and a manageable safety profile” in patients with relapsed or refractory follicular lymphoma, according to results from the phase II ROSEWOOD study.

Pier Luigi Zinzani , MD, PhD, of the Università di Bologna in Italy and colleagues conducted the study and published their findings in the Journal of Clinical Oncology.

They conducted the research because the combination was “found to be well tolerated with an early signal of efficacy in a phase Ib study.”

The study included 217 patients with relapsed or refractory follicular lymphoma who received at least two lines of therapy, including a CD20-directed antibody and an aklyating agent. The researchers assigned patients in a 2:1 ratio to receive zanubrutinib plus obinutuzumab (n=145) or obinutuzumab alone (n=72). The primary endpoint of the study was the overall response rate (ORR) by independent central review. The secondary end point included duration of response, progression-free survival (PFS), overall survival, and safety. The median follow-up was 20.2 months.

The study met its primary end point, as the ORR was 69% in patients receiving zanubrutinib plus obinutuzumab, significantly higher than the ORR of 46% in those who received obinutuzumab (P=.001). The complete response (CR) rate was 39% in patients receiving the combination and was 19% in those receiving obinutuzumab. The 18-month duration of response rate was 69% in patients receiving the doublet and 42% in those receiving obinutuzumab. The median PFS was 28 months in patients receiving zanubrutinib plus obinutuzumab, significantly higher than the median PFS of 10.4 months in those who received obinutuzumab (P<.001).

Thrombocytopenia, neutropenia, diarrhea, and fatigue were the most common adverse events reported in patients receiving zanubrutinib plus obinutuzumab. Atrial fibrillation occurred in 3% of patients and major hemorrhage occurred in 1%.

“The combination of [zanubrutinib plus obinutuzumab] met its primary endpoint of a superior ORR versus [obinutuzumab] and demonstrated meaningful activity and a manageable safety profile in patients with [relapsed or refractory follicular lymphoma],” the study’s authors concluded. “[Zanubrutinib plus obinutuzumab] had a favorable benefit-risk profile compared with [obinutuzumab] and represents a potential combination therapy for patients with [relapsed or refractory follicular lymphoma].”

Reference

Zinzani PL, Mayer J, Flowers CR, et al. ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. 2023. doi:10.1200/jco.23.00775