ROSEWOOD: Zanubrutinib Combo Provides Superior Efficacy in FL

A primary analysis of the phase 2 ROSEWOOD trial finds that a combination of zanubrutinib and obinutuzumab (ZO) is superior to obinutuzumab (O) alone in relapsed/refractory (R/R) follicular lymphoma (FL). Results were presented first at the American Society of Clinical Oncology, held June 2-7, in Chicago, and then at the 2022 European Hematology Association Congress, held June 9-12 in Vienna, Austria.^1,2

Lead investigator Pier Luigi Zinzani, MD, PhD, of the University of Bologna, noted in his presentation in Vienna that FL is the most common subtype of non-Hodgkin lymphoma, but treatment options are limited and, particularly in the third line or later, associated with low rates of long-term disease control. Phase 1b trials showed early signals of efficacy with ZO, leading the investigators to continue with the ROSEWOOD phase 2 trial presented here.

A total of 217 patients who had received at least 2 lines of therapy (including an anti-CD20 antibody and an alkylating agent) were randomized to receive ZO (n = 145) or O (n = 72). The primary end point was overall response rate (ORR) as assessed by independent central review; secondary end points included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

After a median study follow-up of 12.5 months, ORR was 68.3% with ZO vs 45.8% with O (P = .0017), signifying that the study met its primary end point. The secondary outcomes also favored ZO vs O: CRR, 37.2% vs 19.4%, respectively; 18-month DOR rate, 70.9% vs 54.6%; and median PFS, 27.4 months vs 11.2 months. ZO was associated with a 49% reduction of risk of progression or death compared with O. The 18-month probability of OS was 85.4% for the ZO arm and 72.6% for the O arm, although Zinzani noted that the study was not powered to detect significance for this outcome.

Zinzani added that patients’ time to their next antilyphoma treatment was significantly prolonged in the ZO arm. Together, he said, these findings indicate a “deep and durable response” associated with ZO.

An “important point,” according to Zinzani, was that patients receiving O were allowed to cross over to ZO if their disease progressed or if they experienced no response in 12 months. Among the 29 patients who did so, the ORR was 24.1%.

Safety analyses revealed no unexpected findings. The most common adverse events (AEs) in the ZO arm were thrombocytopenia (34.3%) and neutropenia (27.3%); these were also the most common AEs of grade 3 or higher (14.0% and 22.4%, respectively). The rate of treatment-emergent AEs leading to death was lower in the ZO arm than in the O arm (5.6% and 9.9%, respectively).

“ZO demonstrated superior efficacy to O in treatment of [patients] with R/R FL,” the abstract concluded. “ZO had a favorable benefit-risk profile and represents a potential combination therapy for [patients] with R/R FL.”

References
1. Zinzani PL, Mayer J, Auer R, et al. Zanubrutinib plus obitnutuzumab (ZO) versus Obinutuzumab (O) monotherapy in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): primary analysis of the phase 2 randomized ROSEWOOD trial. J Clin Oncol 2022;40(16_suppl): Abstr 7510. doi: 10.1200/JCO.2022.40.16_suppl.7510

2. Zinzani PL, Mayer J, Auer R, et al. Zanubrutiniv + obinutuzumab (ZO) vs obinutuzumab (O) monotherapy in patients (Pts) with relapsed or refractory (R/R) follicular lymphoma (FL): primary analysis of the phase 2 randomized ROSEWOOD trial. HemaSphere. 2022;6(suppl 3):S205.