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

Pan-Mutant Selective PI3Kα Inhibitor

LY4064809 (STX-478)

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