The FDA has granted breakthrough therapy designation to the selective Bruton tyrosine kinase inhibitor orelabrutinib for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL).
This decision is based on results from a phase II trial (NCT04014205) evaluating the safety and efficacy of oral orelabrutinib in 80 patients with B-cell malignancies, including relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). At a median follow-up of 6.3 months (range = 0.4-13.7), 78 patients were evaluable for response, with an overall response rate of 88.5% (n=69). One patient achieved a complete response, while 39 had a partial response (PR) and 29 achieved PR with lymphocytosis. The six-month duration of response (DOR) rate was 89.8%. Median DOR was not yet reached. Disease control rate was 96.2%, with 7.7% of patients experiencing disease stability.
Common grade ≥3 adverse events were neutropenia, thrombocytopenia, and lung infections. At least one serious toxicity was reported in 31% of patients, including decreased platelet count (n=3), pneumonitis (n=2), pyrexia (n=2), and herpes zoster (n=1).
In December 2020, orelabrutinib was approved by the China National Medical Products Administration for the treatment of patients with relapsed/refractory MCL and CLL/SLL.