Follow-up Studies Explore Pirtobrutinib in Chronic Lymphocytic Leukemia

Catherine Callaghan Coombs, MD, an assistant professor of medicine, Division of Hematology, at University of North Carolina (UNC) School of Medicine, UNC Lineberger Comprehensive Cancer Center, discusses 2 upcoming trials in patients with chronic lymphocytic leukemia (CLL).

The phase 3 trials follow the BRUIN study (NCT03740529) and are designed to test the efficacy of pirtobrutinib (LOXO-305) in patients with CLL and small lymphocytic lymphoma (SLL).

Pirtobrutinib is a highly selective oral Bruton’s tyrosine kinase (BTK) inhibitor that binds to BTK to prevent B-cell receptor signaling, reducing tumor growth. It is effective even against tumors that are resistant to ibrutinib (Imbruvica) and acalabrutinib (Calquence). The phase 1/2 BRUIN study of pirtobrutinib found that it had a positive overall response rate of 62% for patients with CLL/SLL and no correlation to grade 3 treatment-related adverse events, according to data published in The Lancet.

Now, the phase 3 randomized BRUIN-313 study (NCT05023980) will compare pirtobrutinib alone versus bendamustine (Bendeka) plus rituximab (Rituxan) in 250 previously untreated patients with CLL/SLL to evaluate progression-free survival (PFS) for up to 5 years. The phase 3 randomized BRUIN-322 study (NCT04965493) compares pirtobrutinib plus venetoclax (Venclexta) and rituximab with venetoclax and rituximab alone in 600 previously treated patients with CLL/SLL to assess PFS over up to 5 years.

Both studies will investigate other end points about the performance of pirtobrutinib including overall survival, overall response rate, and duration of response over a longer period compared with the BRUIN study which ran for up to 2 years.

TRANSCRIPTION:

0:08 | A number of phase 3 trials are planned. In the relapsed/refractory setting, 2 studies will be conducted. First is pirtobrutinib as a monotherapy in comparison with best available therapy, investigator’s choice, which is bendamustine plus rituximab or idelalisib [Zydelig] plus rituximab. The other study is looking at pirtobrutinib in combination with venetoclax and rituximab compared with venetoclax and rituximab alone. It will be exciting to see how those trials progress over time, how the drug performs with longer follow-up, and whether the safety signal continues to be as promising with longer follow-up.