Eli Lilly oncology unit announces updated data from BRUIN trial

[email protected], the oncology unit of Eli Lilly and Company announced updated clinical data from the pirtobrutinib global Phase 1/2 BRUIN trial in patients with chronic lymphocytic leukemia, or CLL, small lymphocytic lymphoma, or SLL, mantle cell lymphoma, or MCL, Richter transformation, or RT, and Waldenstrom macroglobulinemia, or WM. Pirtobrutinib is an investigational, highly selective, reversible inhibitor of Bruton’s tyrosine kinase, or BTK. These data are featured in oral and poster presentations at the 2022 American Society of Hematology, or ASH, annual meeting. The BRUIN Phase 1/2 clinical trial is evaluating pirtobrutinib monotherapy in patients previously treated for MCL, CLL/SLL, or other non-Hodgkin lymphomas, or NHL. The efficacy data being presented at ASH for MCL and CLL/SLL are based on independent review committee, or IRC, assessment while the efficacy data for RT and WM are based on investigator response assessments. The safety cohort consisted of all patients with B-cell malignancies who received at least one dose of pirtobrutinib monotherapy as of the data cutoff date. The BRUIN trial includes one of the largest prospective cohorts of BTK inhibitor pre-treated CLL/SLL patients ever studied. As of the July 29, 2022 data cutoff date, 247 patients with CLL/SLL had received a prior BTK inhibitor and enrolled prior to November 5, 2021, to ensure adequate follow-up. Patients had received a median of three prior therapies. In this dataset, pirtobrutinib demonstrated an overall response rate of 82% and median progression-free survival of 19.6 months. In patients treated with both a prior BTK and BCL2 inhibitor, the ORR was 79%, and median PFS was 16.8 months. Response rates were consistent across all subgroups analyzed regardless of mutation status, age, or previous therapies. As of the January 31, 2022 data cutoff date, the primary analysis set consisted of the first 90 patients enrolled with MCL who had received a prior BTK inhibitor. Patients had received a median of three prior lines of therapy. In this dataset, pirtobrutinib demonstrated an ORR of 58%, a median duration of response of 21.6 months and a median PFS of 7.4 months. Response rates were consistent regardless of number of prior lines of therapy and classes of prior therapy received. The BRUIN trial also includes one of the largest prospective RT populations ever studied. As of the July 29 data cutoff date, 75 patients with RT were response evaluable, with 68 patients having received prior treatment for RT. Among these patients, the median number of prior lines of CLL therapy was two and the median number of prior lines of RT therapy was two. The ORR for the 75 response-evaluable patients was 52% and for the 68 patients previously treated for RT, the ORR was 50%. Among all response evaluable patients, median overall survival, or OS, was 13.1 months and DoR was 5.6 months, regardless of prior RT therapy. As of the July 29 data cutoff date, 80 patients with WM were response evaluable, with 63 patients having received prior treatment with a BTK inhibitor. Among the 63 patients, the median number of prior therapies was three. The major response rate was 67%, including 15 very good partial responses and 27 partial responses. In patients who previously received both chemoimmunotherapy and a covalent BTK inhibitor, the MRR was 68%. Median PFS was 19.4 months in patients who received previous treatment with a covalent BTK inhibitor. In the safety cohort of all pirtobrutinib-treated patients, the most frequent treatment-emergent adverse events, regardless of attribution, were fatigue, diarrhea and contusion. The most frequent Grade 3 TEAE was neutropenia. Low rates of Grade 3 TEAEs of hypertension, hemorrhage and atrial fibrillation/flutter were observed. Overall, discontinuations due to a treatment-related adverse event occurred in 3% of all patients. The safety profile was generally consistent across the populations studied. The safety and tolerability of pirtobrutinib monotherapy in patients with relapsed or refractory B-cell malignancies who were intolerant to a prior covalent BTK inhibitor was evaluated. Atrial fibrillation was among the most common adverse events that led to the discontinuation of a prior covalent BTK inhibitor, and in these patients, this AE recurred with pirtobrutinib treatment in two patients. Most patients did not experience high-grade recurrence of the other common AEs that led to discontinuation of a prior covalent BTK inhibitor, with the exception of neutropenia. No patient who discontinued a prior BTK inhibitor due to an AE had to discontinue pirtobrutinib for the same AE.