Jaypirca (pirtobrutinib)

Pirtobrutinib demonstrated superiority over BendaR in IRC-assessed PFS in treatment-naïve CLL/SLL. OS trends favored pirtobrutinib despite the study design allowing for crossover. Pirtobrutinib was well tolerated, consistent with its known safety profile, and more favorable than BendaR.

The combination of the B-cell lymphoma 2 inhibitor venetoclax with CIT has emerged as a new first-line benchmark with promising response rates and overall survival...Pirtobrutinib has demonstrated responses even in heavily pretreated patients...For R/R disease, novel BTK inhibitors, bispecific antibodies, and cellular therapies are demonstrating substantial efficacy. Ongoing trials investigating combinations of these agents are poised to further transform RT management.

P2, N=29, Recruiting, The First Affiliated Hospital of Soochow University

P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center

P1/2, N=48, Recruiting, Australasian Leukaemia and Lymphoma Group (ALLG) | Not yet recruiting --> Recruiting

The PBPK model captured the clinically observed interactions for itraconazole, rifampin, and midazolam, with predicted pirtobrutinib and midazolam AUC ratios within 0.91- to 1.16-fold of observed. Furthermore, the predicted pirtobrutinib AUC ratios were within 0.51-0.86 with moderate and weak CYP3A4 inducers. The predicted effects of CYP3A4 modulators on pirtobrutinib pharmacokinetics, together with the known exposure-response relationships for safety and efficacy in patients with hematological malignancies, were used for recommending appropriate dosing regimens during coadministration.

Historically, high-dose methotrexate- or cytarabine-based chemotherapy, intrathecal therapy, and radiotherapy have been used; however, responses varied, and toxicity was considerable...Retrospective data support durable responses with ibrutinib, tirabrutinib, and zanubrutinib, while early findings suggest that non-covalent BTK inhibitors expand options for relapsed or refractory cases. Herein, we synthesize current evidence on epidemiology, pathophysiology, and diagnostic work-up. We also outline therapeutic recommendations integrating the genotype, disease pattern, and patient fitness and conclude with unmet needs and future directions.

P3, N=102, Not yet recruiting, SWOG Cancer Research Network

P4, N=150, Not yet recruiting, Eli Lilly and Company

P1/2, N=3, Terminated, M.D. Anderson Cancer Center | N=44 --> 3 | Trial completion date: Oct 2027 --> Oct 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2027 --> Oct 2025; <75% participation

This study highlights the complex clonal dynamics of BTK mutations in R/R CLL patients undergoing pirtobrutinib treatment, and the extent of resistance without an obvious genomic driver. NCT03740529.

P2, N=56, Not yet recruiting, Fondazione Italiana Linfomi - ETS