Phase 2  | Investigational Drug

BRUIN; NCT03740529


BTK Inhibitor

A Phase 1/2 Study of Oral Pirtobrutinib (LOXO-305) in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin's Lymphoma (NHL)*

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Key Inclusion Criteria
  • Phase 1/2 pirtobrutinib monotherapy: B-cell malignancies that have failed or are intolerant to either ≥2 prior standard of care regimens given in combination or sequentially, OR have received 1 prior BTK inhibitor-containing regimen when a BTK inhibitor is approved as first-line therapy (phase 1) OR with prior treatment defined by phase 2 cohort (phase 2 patients only)
  • Phase 1b arm A: Relapsed/recurrent CLL and venetoclax is appropriate salvage treatment; no prior venetoclax is permitted
  • Phase 1b arm B: Relapsed/refractory CLL and venetoclax + rituximab is appropriate salvage treatment; no prior venetoclax is permitted
  • At least 18 years of age
  • Phase 1/1b: Adequate hematologic function that is responsive to transfusion support for thrombocytopenia or anemia
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Adequate hepatic and renal function
  • Able to receive oral study drug
  • Willing to use conventional and effective birth control
Key Exclusion Criteria
  • Investigational agent or anticancer therapy within 5 half-lives or 14 days, whichever is shorter, prior to planned start of specified study treatment; therapeutic monoclonal antibody treatment must be discontinued ≥4 weeks prior to the first dose of study treatment; no concurrent systemic anticancer therapy is permitted
  • Major surgery within 4 weeks prior to planned start of study treatment
  • Radiotherapy with a limited field of radiation for palliation within 7 days of study treatment
  • Pregnant or breastfeeding
  • Require therapeutic anticoagulation with warfarin
  • Any unresolved ≥ grade 2 toxicities as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 attributed to prior therapy (other than alopecia) at the start of study treatment
  • History of allogeneic or autologous stem-cell transplant or chimeric antigen receptor-modified T-cell therapy within the past 60 days prior to planned start of specified study treatment
  • Known central nervous system (CNS) involvement by systemic lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible and enrolled to phase 2 cohort 7 if a compelling clinical rationale is provided by the investigator and with documented sponsor approval
  • Active uncontrolled autoimmune cytopenia when new or concomitant therapy was introduced or escalated to maintain adequate blood counts within 4 weeks prior to study enrollment
  • Clinically significant, uncontrolled cardiac or cardiovascular disease, or myocardial infarction within 6 months prior to planned start of study treatment
  • HIV or active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
  • Clinically significant active malabsorption syndrome
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors (phase 1b only)
  • Phase 1b arm A or B: Patients with prior treatment with venetoclax or other BCL-2 inhibitors
  • Active second malignancy unless in remission and with life expectancy >2 years
  • Phase 1b arm B: Prior significant hypersensitivity to rituximab/biosimilar requiring discontinuation, or prior allergic or anaphylactic reaction to rituximab
  • Prior treatment with pirtobrutinib or known hypersensitivity to any component or excipient of pirtobrutinib
This clinical trial is being conducted globally.
Pirtobrutinib is administered PO.
Venetoclax is administered PO.
Rituximab is administered intravenously.
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.