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| Clinical data | |
|---|---|
| Trade names | Brukinsa |
| Other names | BGB-3111 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a620009 |
| License data | |
| Pregnancy category | |
| Routes of administration | By mouth |
| Drug class | Bruton's tyrosine kinase (BTK) inhibitor |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| PDB ligand | |
| Chemical and physical data | |
| Formula | C27H29N5O3 |
| Molar mass | 471.561 g·mol−1 |
| 3D model (JSmol) | |
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Zanubrutinib, sold under the brand nameBrukinsa, is ananticancer medication used for the treatment ofmantle cell lymphoma (MCL),Waldenström's macroglobulinemia (WM),marginal zone lymphoma (MZL), andchronic lymphocytic leukemia (CLL).[6][10][11][12][13] Zanubrutinib is classified as aBruton's tyrosine kinase (BTK) inhibitor.[6] It is givenby mouth.[6]
It was approved for medical use in the United States in November 2019.[14][10][15][16][17] Zanubrutinib is a therapeutic alternative on theWorld Health Organization's List of Essential Medicines.[18]
Zanubrutinib isindicated for the treatment of adults withmantle cell lymphoma who have received at least one prior therapy,[6][10][11] and for the treatment of Waldenström's macroglobulinemia.[19] It is also indicated for the treatment of adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based regimen.[12]
In January 2023, the USFood and Drug Administration (FDA) approved zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma.[20]
In March 2024, FDA granted accelerated approval to zanubrutinib, in combination withobinutuzumab, for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.[21][22]
The most common adverse effects (≥30%) are: decreasedneutrophil count,upper respiratory tract infection, decreasedplatelet count,hemorrhage and musculoskeletal pain.[23]
Efficacy was evaluated in BGB-3111-206 (NCT03206970), a phase II open-label, multicenter, single-arm trial of 86 participants with mantle cell lymphoma (MCL) who received at least one prior therapy.[15] Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity.[15] Efficacy was also assessed in BGB-3111-AU-003 (NCT02343120), a phase I/II, open-label, dose-escalation, global, multicenter, single-arm trial of B‑cell malignancies, including 32 previously treated MCL participants treated with zanubrutinib administered orally at 160 mg twice daily or 320 mg once daily.[15][16]
The primary efficacy outcome measure in both trials was overall response rate (ORR), as assessed by an independent review committee.[15] In trial BGB-3111-206, FDG-PET scans were required and the ORR was 84% (95% CI: 74, 91), with a complete response rate of 59% (95% CI 48, 70) and a median response duration of 19.5 months (95% CI: 16.6, not estimable).[15] In trial BGB-3111-AU-003, FDG-PET scans were not required and the ORR was 84% (95% CI: 67, 95), with a complete response rate of 22% (95% CI: 9, 40) and a median response duration of 18.5 months (95% CI: 12.6, not estimable).[15] Trial 1 was conducted at 13 sites in China, and Trial 2 was conducted at 25 sites in the United States, United Kingdom, Australia, New Zealand, Italy, and South Korea.[16]
The U.S.Food and Drug Administration (FDA) granted zanubrutinibpriority review,accelerated approval,breakthrough therapy, andorphan drug designations.[10][15][24] The FDA approved zanubrutinib in November 2019, and granted the application for Brukinsa to BeiGene USA Inc.[10][15][25]
In August 2021, the FDA approved zanubrutinib for the treatment of Waldenström's macroglobulinemia and in September 2021, for marginal zone lymphoma (MZL).[19][26][8][12][27]
Zanubrutinib was investigated for Waldenström's macroglobulinemia in ASPEN (NCT03053440), a randomized, active control, open-label trial, comparing zanubrutinib andIbrutinib in participants with MYD88 L265P mutation (MYD88MUT) WM.[19] Participants in Cohort 1 (n=201) were randomized 1:1 to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity.[19] Cohort 2 enrolled participants with MYD88 wildtype (MYD88WT) or MYD88 mutation unknown WM (n=26 and 2, respectively) and received zanubrutinib 160 mg twice daily.[19]
Approval of zanubrutinib for marginal zone lymphoma is based on two open-label, multicenter, single-arm trials: BGB-3111-214 (NCT03846427), which evaluated 66 participants with MZL who received at least one prior anti-CD20-based therapy, and BGB-3111-AU-003 (NCT02343120), which included 20 participants with previously treated MZL.[12]
In March 2024, the FDA granted accelerated approval to zanubrutinib with obinutuzumab for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.[21] The regimen was evaluated in Study BGB-3111-212 (ROSEWOOD; NCT03332017), an open-label, multicenter, randomized trial that enrolled 217 adult participants with relapsed or refractory follicular lymphoma after at least two prior systemic treatments.[21] Participants were randomized (2:1) to receive either zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity plus obinutuzumab (ZO), or obinutuzumab alone.[21] The median number of prior lines of therapy was 3 (range 2-11).[21] The application was grantedfast track and orphan drug designations.[21]
In September 2021, theCommittee for Medicinal Products for Human Use (CHMP) of theEuropean Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Brukinsa, intended for the treatment of Waldenström's macroglobulinaemia.[28] The applicant for this medicinal product is BeiGene Ireland Ltd.[28] Zanubrutinib was approved for medical use in the European Union in November 2021.[7][29]
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