Tirabrutinib Well-Tolerated as Combo or Monotherapy for Pretreated CLL

Therapy with tirabrutinib alone or plus idelalisib or entospletinib was shown to be well-tolerated in patients with chronic lymphocytic leukemia (CLL) in an open-label, phase 1b clinical trial (Clin Cancer Res. 2020 Mar 10. Epub ahead of print).

“Bruton's tyrosine kinase (BTK) inhibition alone leads to incomplete responses in [CLL]. Combination therapy may reduce activation of escape pathways and deepen responses,” according to lead investigator Alexey V. Danilov, MD, PhD, City Of Hope National Medical Center, Duarte, California, and colleagues.

Thus, Dr Danilov et al conducted a study to examine the safety, tolerability, pharmacokinetics, and preliminary efficacy of the BTK inhibitor tirabrutinib administered as monotherapy or in combination with idelalisib or entospletinib in patients with relapsed/refractory CLL.

A total of 53 patients with relapsed/refractory CLL were included in the study and given tirabrutinib 80 mg alone once daily or tirabrutinib 20 mg to 150 mg once daily plus idelalisib at a dose of 50 mg twice daily or 100 mg once daily or entospletinib at a dose of 200 mg or 400 mg once daily.

According to the findings, exposure to systemic tirabrutinib was comparable between all treatment arms, with no maximum tolerated dose defined. The most frequently reported adverse event across all treatment arms was diarrhea (43%, 1 patient grade ≥3), and therapy discontinuation due to adverse events was rare (13%).

Among recipients of tirabrutinib monotherapy, tirabrutinib plus delalisib, and tirabrutinib plus entospletinib, objective response rates were 83%, 93%, and 100%, respectively; complete responses were 7%, 7%, and 10%, respectively.

“[Tirabrutinib plus idelalisib or entospletinib] was well tolerated in patients with CLL, establishing an acceptable safety profile for concurrent selective inhibition of BTK with either PI3Kδ or SYK,” Dr Danilov and colleagues said.

“This small study did not establish a superior efficacy of the combinations over [tirabrutinib] alone,” they concluded.—Hina Porcelli