FDA Grants Accelerated Approval to Zanubrutinib for Marginal Zone Lymphoma

Zanubrutinib has received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) previously treated with at least one anti-CD20-based regimen.

Accelerated approval is based on efficacy data from the phase II MAGNOLIA trial and the phase I/II BGB-3111-AU-003 trial, with overall response rate (ORR) as assessed by independent review committee per 2014 Lugano Classification as the primary endpoint. Additional endpoints were complete response (CR) rate and duration of response (DOR).

In the phase II MAGNOLIA trial, 66 evaluable patients had the following subtypes of relapsed/refractory MZL:

· extranodal (n=26)

· nodal (n=26)

· splenic (n=12)

· unknown (n=4)

The ORR, based on CT scan assessment, was 56% (95% CI 43-68%). The CR rate using CT scan was 20%. Based on assessment using PET-CT scan, the ORR was 67% (95% CI 54-78%) and the CR rate was 26%. At a median follow-up of 8.3 months, median DOR was not reached. At 12 months, 85% of responders were still in remission (95% CI 67-93%). Responses were observed across all subtypes.

A total of 20 patients were evaluated in the BGB-3111-AU-003 trial, including the following subtypes:

· extranodal (n=9)

· nodal (n=5)

· splenic (n=6)

The ORR and CR rates based on CT scan assessment were 80% (95% CI 56-94%) and 20%, respectively. The median DOR was not reached at a median follow-up of 31.4 months. At 12 months, 72% of responders were still in remission (95% CI 40-88%).

Common adverse events (AEs) occurring in ≥30% of the 847 patients in the pooled safety population were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain.

Recommended dosing for this indication is either 160 mg twice daily or 320 mg once daily orally with or without food. The dose may be reduced for patients with severe hepatic impairment and certain drug interactions.

Source: BeiGene press release, September 15, 2021.