FDA grants accelerated approval to zanubrutinib for relapsed or refractory follicular lymphoma

Regulatory approval: On March 7, 2024, the FDA granted accelerated approval to zanubrutinib (Brukinsa) in combination with obinutuzumab for adults with relapsed or refractory follicular lymphoma after ≥2 prior lines of systemic therapy. Approval was supported by the open-label, randomized ROSEWOOD trial (NCT03332017), where overall response rate was 69% with zanubrutinib+obinutuzumab vs 46% with obinutuzumab alone; median duration of response was not reached vs 14.0 months, respectively.

FDA accelerated approval: zanubrutinib + obinutuzumab in R/R follicular lymphoma

Type: Regulatory approval (accelerated approval)
Date: 2024-03-07
Agency: US FDA

The FDA granted accelerated approval to zanubrutinib (Brukinsa) in combination with obinutuzumab for relapsed or refractory follicular lymphoma in adults after two or more lines of systemic therapy.

Supporting trial (ROSEWOOD; BGB-3111-212; NCT03332017)

  • Design: Open-label, multicenter, randomized trial (2:1)
  • Population: 217 adults with R/R FL after ≥2 prior systemic therapies; median prior lines 3 (range 2–11)
  • Arms: zanubrutinib 160 mg PO BID until progression/toxicity + obinutuzumab (ZO) vs obinutuzumab alone
  • Endpoints (IRC-assessed): overall response rate (ORR) and duration of response (DOR)

Efficacy:

  • ORR: 69% (95% CI 61–76) with ZO vs 46% (95% CI 34–58) with obinutuzumab; p=0.0012
  • Median follow-up: 19.0 months
  • Median DOR: not reached (95% CI 25.3 months, NE) with ZO vs 14.0 months (95% CI 9.2–25.1)
  • Estimated 18-month DOR rate (ZO): 69% (95% CI 58–78)

Safety and dosing

Across zanubrutinib trials, common adverse reactions (≥30%; incl. lab abnormalities) included decreased neutrophils (51%), decreased platelets (41%), URTI (38%), hemorrhage (32%), and musculoskeletal pain (31%). Serious adverse reactions occurred in 35% of FL patients receiving ZO. Recommended dosing: 160 mg BID or 320 mg QD until progression or unacceptable toxicity.

The application received fast track and orphan drug designations.

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