FDA Approves Tablet Formulation of Zanubrutinib for B-Cell Malignancies

FDA

The FDA has approved a tablet formulation of zanubrutinib (Brukinsa) for use in all 5 approved indications of the capsule formulation.1

Zanubrutinib was previously approved for the treatment of adult patients with:2

• Mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
• Waldenström’s macroglobulinemia
• Relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 anti-CD20–based regimen.
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
• Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.

“[Zanubrutinib's] leadership in the United States underscores the trust physicians and patients have placed in its differentiated clinical profile,” Matt Shaulis, general manager of North America at BeOne, stated in a news release.1 “With this new tablet formulation, we are making treatment simpler and more convenient—an important step forward for patients facing certain B-cell cancers.”

The recommended dose of the tablet formulation mirrors the capsule formulation at 320 mg per day. The tablets are each 160 mg, allowing patients to receive 2 tablets vs 4 80-mg capsules.

Key Safety Information for Zanubrutinib

Pooled safety data from 11 clinical trials, including 9 monotherapy studies and 2 combination trials, the most common adverse effects reported in at least 30% of patients comprised decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

The label for zanubrutinib includes warnings and precautions for hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, hepatotoxicity (including drug-induced liver injury), and embryo-fetal toxicity.

Zanubrutinib's Most Recent Indication

In March 2024, the FDA granted accelerated approval to zanubrutinib in combination with obinutuzumab for patients with relapsed or refractory follicular lymphoma after 2 or more lines of systemic therapy.3

That regulatory decision was based on data from the phase 2 ROSEWOOD trial (NCT03332017). At a median follow-up of 20.2 months, patients treated with the combination (n = 145) achieved an overall response rate (ORR) of 69% (95% CI, 60.8%-76.4%) vs 46% (95% CI, 34%-58%) for obinutuzumab alone (n = 72; two-sided P = .0012).4 The zanubruinib regimen generated a complete response (CR) rate of 39.3% compared with 19.4% for obinutuzumab alone (P = .0035).

The median duration of response (DOR) was not estimable (NE; 95% CI, 25.3 months–NE) with the combination vs 14.0 months (95% CI, 9.2-25.1) for obinutuzumab alone. The median duration of CR (DOCR) was NE (95% CI, 26.5-NE) vs 26.5 months (95% CI, 2.7-NE), respectively.

Patients experienced 18-month DOR rates of 69.3% (95% CI, 57.8%-78.2%) when treated with zanubrutinib/obinutuzumab vs 41.9% (95% CI, 22.6%-60.1%) for obinutuzumab monotherapy. The 18-month DOCR rates were 87.4% (95% CI, 73.8%-94.2%) and 51.1% (95% CI, 21.0%-74.9%), respectively.

Safety data from ROSEWOOD showed that the most common any-grade nonhematologic treatment-emergent AEs (TEAEs) included diarrhea (zanubrutinib plus obinutuzumab, 18.2%; obinutuzumab alone, 16.9%), fatigue (15.4%; 14.1%), pyrexia (13.3%; 19.7%), constipation (13.3%; 8.5%), cough (12.6%; 12.7%), asthenia (11.9%; 8.5%), pneumonia (11.9%; 7%), dyspnea (11.2%; 9.9%), back pain (11.5%; 5.6%), COVID-19 (9.8%; 9.9%), nausea (9.1%; 14.1%), abdominal pain (7.7%; 11.3%), pruritis (7%; 9.9%), and infusion-related reaction (2.8%; 9.9%).

Grade 3 or higher nonhematologic TEAEs comprised pneumonia (zanubrutinib plus obinutuzumab, 9.8%; obinutuzumab alone, 4.2%), COVID-19 (5.6%; 2.8%), COVID-19–related pneumonia (3.5%; 2.8%), diarrhea (2.8%; 1.4%), febrile neutropenia (2.1%; 1.4%), atrial fibrillation (1.4%; 0%), infusion-related reaction (0.7%; 4.2%), and hypertension (0.7%; 1.4%).

References

1. U.S. FDA approves tablet formulation of BeOne’s Brukinsa for all approved indications. News release. BeOne. June 11, 2025. Accessed June 11, 2025. https://www.businesswire.com/news/home/20250611860939/en/U.S.-FDA-Approves-Tablet-Formulation-of-BeOnes-BRUKINSA-for-All-Approved-Indications
2. Brukinsa. Prescribing information. BeOne. Updated June 2025. Accessed June 11, 2025. https://beonemedicines.us/PDF/BRUKINSAUSPI.pdf
3. FDA grants accelerated approval to zanubrutinib for relapsed or refractory follicular lymphoma. News release. FDA. March 7, 2024. Accessed June 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanubrutinib-relapsed-or-refractory-follicular-lymphoma
4. Flowers C, Zinzani PL, Mayer J, et al. Zanubrutinib plus obinutuzumab versus obinutuzumab in patients with relapsed/refractory follicular lymphoma: Updated analysis of the ROSEWOOD study. J Clin Oncol. 2023;41(suppl 16):7545. doi:10.1200/JCO.2023.41.16_suppl.7545