Zanubrutinib Plus Obinutuzumab for R/R Follicular Lymphoma Receives FDA Acceptance of sNDA

Zanubrutinib Plus Obinutuzumab for R/R Follicular Lymphoma Receives FDA Acceptance of sNDA

Source – BeiGene

BeiGene has announced that the FDA has accepted a supplemental new drug application (sNDA) for the combination of BRUKINSA (zanubrutinib) and obinutuzumab as a treatment for adult patients with relapsed/refractory follicular lymphoma (R/R FL) who have undergone at least two prior lines of therapy. This news follows positive results from the Phase II ROSEWOOD study (NCT03332017), which support the sNDA submission.

The study demonstrated that the combination of zanubrutinib and obinutuzumab provided superior efficacy compared to obinutuzumab alone. At a median follow-up of 12.5 months, the combination treatment achieved an overall response rate (ORR) of 68.3% compared to 45.8% for obinutuzumab alone (P =0.0017). The complete response (CR) rate was also higher at 37.2% versus 19.4% (P = 0.0083) with the combination therapy. Notably, the 18-month landmark duration of response (DOR) for the combination was 69.3%, indicating durable responses.

Longer-term data with a median follow-up of 20.2 months further supported the efficacy of the combination. The ORR was 69.0% for the combination versus 45.8% for obinutuzumab monotherapy (P = 0.0012). Additionally, the combination treatment reduced the risk of disease progression or death by 50% compared to obinutuzumab alone (HR, 0.50; 95% CI, 0.33-0.75).

The safety profile of the combination therapy was consistent with previous studies evaluating both agents. The most common treatment-emergent adverse events (AEs) observed in the combination arm were diarrhea (18.2% vs 16.9% in the obinutuzumab alone arm), fatigue (15.4% vs 14.1%), and pyrexia (13.3% vs 19.7%).

Zanubrutinib is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) and is being evaluated globally as a monotherapy and in combination with other therapies for the treatment of various B-cell malignancies. The agent is designed to provide complete and sustained inhibition of the BTK protein through optimal bioavailability, half-life, and selectivity. Zanubrutinib has demonstrated the inhibition of malignant B cell proliferation across multiple disease-relevant tissues, distinguishing it from other approved BTK inhibitors.

The FDA has assigned a target action date for the first quarter of 2024 under the Prescription Drug User Fee Act.

The ongoing Phase II ROSEWOOD study is an open-label, randomized trial comparing the combination of zanubrutinib with obinutuzumab versus obinutuzumab monotherapy in patients with R/R FL who have received two or more prior lines of therapy. A total of 217 patients with pretreated R/R non-Hodgkin FL were enrolled, with 145 receiving the combination treatment and 72 receiving obinutuzumab monotherapy.

The primary endpoint of the study is ORR assessed by independent central review (ICR) according to the Lugano classification. Secondary endpoints include investigator-assessed ORR, DOR, progression-free survival, overall survival, and safety analysis.

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