Efficacy of Pirtobrutinib in CLL/SLL

Video

Catherine Callaghan Coombs, MD, discusses the results of the phase 1/2 BRUIN study of pirtobrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia.

Catherine Callaghan Coombs, MD, an assistant professor of medicine in the Division of Hematology at the University of North Carolina School of Medicine, discusses the results of the phase 1/2 BRUIN study (NCT03740529) of pirtobrutinib (LOXO-305) in chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL).

According to Coombs, pirtobrutinib is a non-covalent inhibitor of BTK and is given as a once-daily oral drug. The BRUIN study was designed using a 3+3 dose escalation scheme. Safety data found that the agent was very well tolerated with relatively little grade 3 adverse events. Atrial fibrillation and bleeding, serious adverse events associated with BTK inhibitors, were rarely seen with pirtobrutinib.

The population was heavily pretreated, with the median prior lines of therapy in the general population being 4. For patients who received a prior BTK inhibitor, the median prior lines of therapy were 4. The overall response rate was 63% in the general population and 62% in the population who received a prior BTK inhibitor. Additionally, response rate increased with time, with the overall response at 10-months being 80%.

0:08 | This is a unique drug in that it is a non-covalent inhibitor of BTK, distinguishing it from the prior agents that target BTK. The drug was given as a once daily oral drug. We ramped it up in a standard 3+3 fashion. A few unique features are that the drug was allowed to be dose escalated and doses previously were deemed safe. And it was also allowed to expand cohort levels for doses previously deemed safe.

0:43 | The drug was exceptionally well tolerated with very few grade 3 events. The class effect, side effects that are of course, worrisome, in patients on BTK inhibitors, such as atrial fibrillation and bleeding, were rarely if ever seen. And 2 atrial fibrillation events were actually in patients who'd previously had atrial fibrillation. And so those were deemed unrelated. So overall, very well tolerated. And as far as efficacy goes, the drug performed very well in this heavily pretreated cohort. So, the median number of lines of prior therapy was 3, it was 4 when we look at patients who had had a prior BTK inhibitor and the overall response rate was 63%. It was actually very similar in that subset that it had prior BTK inhibitors at 62%. The other remarkable thing is that the response rate increased over time. And so, in patients that had been on the drug for over 10 months, the response rate was above 80%. The majority of responses were PRs, and there were also a number of PRLs, and most patients are ongoing with very few having discontinued due to progressive disease.

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