Global pharma company Eli Lilly’s drug has delivered a dramatic win in a head-to-head Phase 3 trial, slashing the risk of disease progression or death by 80% in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) patients.
The company has unveiled the results of pirtobrutinib from its BRUIN CLL-313 study, positioning the non-covalent BTK inhibitor as a potential new front-line standard.
"The results from BRUIN CLL-313 show a significant effect size, among the most pronounced ever observed for a single agent BTK inhibitor in a front-line CLL study," said Wojciech Jurczak, of the Maria Sklodowska-Curie National Research Institute of Oncology in Krakow, Poland.
"The magnitude of the progression-free survival benefit, early overall survival trend and safety profile observed in BRUIN CLL-313 offer highly compelling evidence for the potential role of pirtobrutinib in treatment-naïve CLL."
The trial enrolled 282 untreated CLL/SLL patients without del(17p) and randomized them to pirtobrutinib monotherapy or standard bendamustine plus rituximab (BR).
After a median 28.1-month follow-up, pirtobrutinib showed overwhelming superiority, with the primary endpoint of progression-free survival significantly favoring the drug across every pre-specified subgroup, including those with high-risk genetic features.
Overall survival data remain immature, but the trial still showed an early trend toward benefit—despite more than half of BR-treated patients crossing over to pirtobrutinib after their disease progressed.
Patients on Lilly’s drug experienced far fewer severe side effects: grade ≥3 events occurred in 40% of those on pirtobrutinib versus 67.4% on BR. Dose reductions and treatment discontinuations due to adverse events were also markedly lower.
Strikingly, rates of atrial fibrillation—often a concern with BTK inhibitors—were nearly identical between arms, even though BR is not known to increase the risk.
"These findings support the potential use of pirtobrutinib in certain treatment-naïve patients and underscore its unique position as the only BTK inhibitor to show promise in treating both newly diagnosed patients with CLL or SLL and those who have progressed on a covalent BTK inhibitor," said Jacob Van Naarden, executive vice president and president of Lilly Oncology.
"Alongside the recently presented BRUIN-CLL 314 results, we are excited about how collectively these data may advance the therapeutic landscape in treatment-naïve CLL and are hopeful we will receive regulatory approvals for pirtobrutinib in earlier disease settings sometime next year, further expanding treatment options for patients."
