Loxo@Lilly Presents Updated Pirtobrutinib Data from the Phase 1/2 BRUIN Clinical Trial at the 2022 American Society of Hematology Annual Meeting
Pirtobrutinib demonstrates activity across covalent BTK inhibitor pre-treated B-cell malignancies and multiple patient subgroups
"These data presented at ASH build on previous results with significantly longer follow-up and continue to expand on the body of evidence supporting pirtobrutinib as a potential treatment option for patients previously treated with a covalent BTK inhibitor across a range of B-cell malignancies," said
"We continue to be very excited by the results of pirtobrutinib across B-cell malignancies," said
Key Data at ASH
The BRUIN Phase 1/2 clinical trial is evaluating pirtobrutinib monotherapy in patients previously treated for MCL, CLL/SLL, or other non-Hodgkin lymphomas (NHL). The efficacy data being presented at ASH for MCL and CLL/SLL are based on independent review committee (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.
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
The BRUIN trial includes one of the largest prospective cohorts of BTK inhibitor pre-treated CLL/SLL patients ever studied. As of the
Mantle Cell Lymphoma (MCL)
As of the
Richter Transformation (RT)
The BRUIN trial also includes one of the largest prospective RT populations ever studied. As of the
Waldenström Macroglobulinemia (WM)
As of the
Safety of Pirtobrutinib from the BRUIN Study
In the safety cohort of all pirtobrutinib-treated patients (n=773), the most frequent treatment-emergent adverse events (TEAE) (≥15%), regardless of attribution, were fatigue (29%), diarrhea (24%), and contusion (19%). The most frequent Grade ≥3 TEAE was neutropenia (20%). Low rates of Grade ≥3 TEAEs of hypertension (9%), hemorrhage (11%), and atrial fibrillation/flutter (3%) were observed. Overall, discontinuations due to a treatment-related adverse event occurred in 3% (n=20) of all patients. The safety profile was generally consistent across the populations studied.
Safety and Tolerability in Covalent BTK Intolerant Patients
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 (n=127) was evaluated. Atrial fibrillation was among the most common adverse events (AE) that led to the discontinuation of a prior covalent BTK inhibitor, and in these patients (n=30), 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 (in the patients in whom neutropenia recurred, 67% were Grade ≥3). No patient who discontinued a prior BTK inhibitor due to an AE had to discontinue pirtobrutinib for the same AE.
Loxo@Lilly is studying pirtobrutinib in multiple Phase 3 studies. Details on the trials can be found at lillyloxooncologypipeline.com or by visiting clinicaltrials.gov.
About Pirtobrutinib (LOXO-305)
Pirtobrutinib is an investigational, highly selective, reversible (non-covalent) Bruton's tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM). Pirtobrutinib was developed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, and preserve activity in the presence of the C481 acquired resistance mutations. Pirtobrutinib was found to be highly selective – 300 times more selective in BTK inhibition versus 98% of other kinases tested in preclinical studies. Interested patients and physicians can contact the Loxo@Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email firstname.lastname@example.org.
About the BRUIN Phase 1/2 Trial
The BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of pirtobrutinib in patients previously treated for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or other non-Hodgkin lymphomas (NHL).
The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by overall response rate (ORR) for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an independent review committee (IRC). Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, and PK.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about pirtobrutinib as a potential treatment for people with previously treated chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, Richter transformation, and Waldenström macroglobulinemia and the timeline for future readouts, presentations, and other milestones relating to pirtobrutinib and its clinical trials, and reflects
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