Eli Lilly and Company has reported results from the BRUIN CLL-322 Phase III trial, assessing Jaypirca (pirtobrutinib), a non-covalent bruton tyrosine kinase (BTK) inhibitor, combined with venetoclax and rituximab against venetoclax and rituximab alone in patients with relapsed or refractory (r/r) chronic lymphocytic leukaemia or small lymphocytic lymphoma (CLL/SLL).
The global, open-label trial met its primary endpoint and demonstrated a reduction in the risk of disease progression or death by 45% when compared with the control group.
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It included 639 patients, 79.8% of whom had previously received covalent BTK inhibitors. Participants were randomised equally to receive either pirtobrutinib plus venetoclax and rituximab (PVR) or venetoclax and rituximab alone (VR).
PVR patients received three cycles of pirtobrutinib and rituximab before venetoclax introduction.
At a median follow-up of 27.3 months and using a data cutoff, independent review committee (IRC)-assessed progression-free survival (PFS) was significantly improved in the PVR group.
The median PFS was not reached for the PVR group while it was 39.7 months for the VR group.
The benefit was consistent across subgroups, including those with prior exposure to covalent BTK inhibitors and patients who discontinued covalent BTK inhibitors due to disease progression.
It was also observed in individuals with high-risk features such as unmutated immunoglobulin heavy chain variable region, TP53 mutations, 17p deletions, or complex karyotype.
Exploratory analysis in second-line patients indicated a PFS advantage for the PVR regimen.
Overall survival was not mature at the time of analysis, with final assessment planned for a future date. The secondary endpoint, time to next treatment, also favoured PVR.
Safety findings showed rates of Grade ≥3 adverse events were similar between groups. Grade ≥3 clinical adverse events of interest included neutropenia and tumour lysis syndrome, with discontinuation rates due to adverse events comparable across arms.
Lilly oncology executive vice-president and president Jacob Van Naarden said: “These remarkable findings support the potential addition of two years of Jaypirca to a time-limited venetoclax-based regimen in r/r CLL.
“BRUIN CLL-322 enrolled a mostly covalent BTK inhibitor-pretreated population, ensuring that these results have applicability to the modern CLL treatment landscape where covalent BTK inhibitor use is now common.”
Lilly intends to submit these results to global regulatory authorities and is further studying Jaypirca in CLL/SLL in multiple Phase III studies.
Last month, the company reported positive interim results from the ongoing Phase Ib Heart-2 clinical trial of VERVE-102, an investigational therapy intended as a one-time treatment for hypercholesterolaemia.
