Orelabrutinib receives approval in China for the treatment of R/R CLL, SLL, and R/R MCL

On December 27, 2020, orelabrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, received approval from the Chinese National Medical Products Administration (NMPA) for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and R/R mantle cell lymphoma (MCL).¹

This approval was based on data from two phase II clinical trials (NCT03493217 and NCT03494179), which were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.²

Orelabrutinib^1,3

• An orally administered, highly selective, BTK inhibitor for the treatment of cancer and autoimmune diseases.
• Irreversibly binds to BTK and blocks B-cell receptor signaling, which is crucial for the proliferation and survival of leukemic cells.
• Currently being investigated as monotherapy in various R/R B-cell malignancies, including CLL, MCL, marginal zone lymphoma, central nervous system lymphoma, and Waldenström’s macroglobulinemia.
• Also being studied in combination with MIL62, a next-generation CD20 antibody, in patients with follicular lymphoma.

NCT03493217^2,4

• A phase I/II, multicenter, open-label study to evaluate the safety and efficacy of orelabrutinib in Chinese patients with R/R CLL (n = 70) or SLL (n = 10).
• Dosage: 150 mg daily, minimum of 12 cycles.
• Primary endpoint: objective response rate (ORR) assessed by the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria with modifications or the 2014 Lugano criteria, for CLL and SLL, respectively.
• Secondary endpoints: duration of response (DOR), progression-free survival (PFS), and safety.

Results^2,4

• With a median follow-up of 14.3 months, the ORR was 91.3% (with 10.0% complete remission, 63.8% partial remission [PR], and 17.5% PR with lymphocytosis).
• The median DOR and PFS were not yet reached.
• Most adverse events (AEs) were mild to moderate, with no new safety nor toxicity concerns compared with previous results.
• The most frequent AEs included thrombocytopenia, neutropenia, anemia, upper respiratory tract infection, pneumonia, and hypokalemia.

NCT03494179^2,5

• A phase I/II, multicenter, open-label study to evaluate the safety and efficacy of orelabrutinib in Chinese patients with R/R MCL (n = 106).
• Primary endpoint: ORR assessed by the 2014 Lugano criteria.
• Secondary endpoints: DOR, PFS, OS, and safety.
• Dosage: 100 mg twice daily (n = 20) or 150 mg once daily (n = 86).

Results^2,5

• With a median follow-up of 16.4 months, the ORR was 87.9% (with 34.3% complete remission, 53.5% PR, and 6.1% stable disease).
• The median DOR and PFS were not yet reached.
• Grade ≥ 3 treatment-related AEs were reported in 33% of patients and led to a dose reduction or study discontinuation in 6.6% and 2.8% of patients, respectively.
• The most common AEs included thrombocytopenia, neutropenia, leukopenia, and hypertension.