FDA Grants Accelerated Approval to Zanubrutinib for Relapsed, Refractory Marginal Zone Lymphoma

In the MAGNOLIA trial, the median duration of response was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months.

Officials with the FDA have granted accelerated approval to zanubrutinib (Brukinsa, BeiGene) for the treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 anti-CD20-based regimen.

Zanubrutinib, a small molecule inhibitor of Bruton’s tyrosine kinase (BTK), is being investigated as a monotherapy and in combination with other therapies for various B-cell malignancies. The approval is based on overall response rate (ORR) data from 2 single-arm clinical trials. Continued approval may be contingent upon findings from a confirmatory trial, according to a press release.

“BTK plays a critical role in B-cell receptor signaling, a driver in the development of marginal zone lymphoma,” said Stephen Opat, FRACP, FRCPA, MBBS, director of clinical hematology at Monash Health and lead principal investigator of the MAGNOLIA trial, in the press release. “In the MAGNOLIA trial, Brukinsa demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes. In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions.”

The multicenter, pivotal phase 2 MAGNOLIA trial evaluated zanubrutinib in 66 patients with relapsed or refractory MZL, including 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and 4 with unknown subtype. Based on assessment using a CT scan, the overall response rate was 56% with a complete response rate of 20%. With assessment prioritizing PET-CT scan, the ORR was 67% with a complete response rate of 26%.

The median duration of response was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months. Notably, responses were observed in all MZL subtypes.

The global phase 1/2 trial BGB-3111-AU-003 evaluated 20 patients with relapsed or refractory MZL, including 9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype. Based on assessments using CT scans, the ORR was 80% with a complete response rate of 20%. The median duration of response was not reached at the median follow-up time of 31.4 months and 72% of responders were still in remission at 12 months.

“The MAGNOLIA trial results provided additional evidence that the selective design of Brukinsa can be translated to improved treatment outcomes for these patients,” said Jane Huang, MD, chief medical officer of hematology at BeiGene, in the press release. “The ongoing evaluation of Brukinsa in its broad global clinical program will enable us to further understand this potentially best-in-class BTK inhibitor and its impact on patients.”

The most common adverse events in the pooled safety population of 847 patients included decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain. The recommended dose is either 160 mg twice daily or 320 mg once daily, taken orally.

“The approval of Brukinsa offers patients with relapsed and refractory marginal zone lymphoma a new treatment option and new hope for improving patient outcomes,” said Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation, in the press release.

REFERENCE

US FDA Grants Brukinsa (Zanubrutinib) Accelerated Approval in Relapsed or Refractory Marginal Zone Lymphoma. News release. BeiGene; September 15, 2021. Accessed September 15, 2021. https://ir.beigene.com/news-details/?id=0d5b56bb-d6cd-4606-a9bd-f49e85bb113b