Phase 3  | 
 | Investigational Drug

BRUIN CLL-321; NCT04666038


BTK Inhibitor

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*

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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. 
Contact the Loxo Oncology at Lilly Clinical Trial Team

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The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.