BTK Inhibitor
Pirtobrutinib
Phase
3
Enrolling
A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma*
Related Resources:
Key Inclusion Criteria
- Confirmed diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) requiring therapy as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
- Previously treated with a covalent BTK inhibitor
- Eastern Cooperative Oncology Group (ECOG) status of 0-2
- Absolute neutrophil count ≥0.75 × 109/L without granulocyte-colony stimulating factor support
- Hemoglobin ≥8 g/dL not requiring transfusion support or growth factors within 14 days of cycle 1 day 1
- Platelets ≥50 × 109/L not requiring transfusion support or growth factors within 14 days of cycle 1 day 1. If the investigator has chosen rituximab + bendamustine as the arm B treatment, platelets must be ≥75 × 109/L
- AST and ALT ≤3.0 x upper limit of normal (ULN); total bilirubin ≤1.5 x ULN
- Estimated creatinine clearance of ≥30 mL/min
Key Exclusion Criteria
- Known or suspected Richter's transformation at any time preceding enrollment
- Known or suspected history of central nervous system (CNS) involvement by CLL/SLL
- Ongoing drug-induced liver injury
- Active uncontrolled autoimmune cytopenia
- Significant cardiovascular disease
- History of allogeneic or autologous stem cell transplantation (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 60 days
- Active hepatitis B or C
- Known active cytomegalovirus (CMV) infection
- Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
- Known HIV infection, regardless of cluster of differentiation 4 (CD4) count
- Clinically significant active malabsorption syndrome or inflammatory bowel disease
- Prior exposure to a non-covalent (reversible) BTK inhibitor
- Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist
- Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors
- Vaccination with a live vaccine within 28 days prior to randomization
- Patients with the following hypersensitivity:
- Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib, idelalisib, and bendamustine
- Prior significant hypersensitivity to rituximab
*
This clinical trial is being conducted globally.
†
Pirtobrutinib is administered 200 mg PO QD until progression or unacceptable toxicity.
‡
Idelalisib is administered 150 mg PO BID.
§
Rituximab is administered intravenously (IV) as 8 total infusions.
‖
Bendamustine is administered 70 mg/m2 IV on days 1 and 2 of cycles 1-6.
¶
Rituximab is administered IV as 6 total infusions.
