Pirtobrutinib (LOXO-305) and Venetoclax for the Treatment of Patients With CLL or SLL Resistant to Covalent BTKi

Must have received: BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib) — current use

Currently taking ibrutinib, acalabrutinib, or zanubrutinib at any daily dose and tolerating it for > 4 weeks; Evidence of progressive disease by iwCLL 2018 criteria for progressive disease or doubling of absolute lymphocyte count (ALC) in ≤ 6 months while on BTK inhibitor provided ALC is > 5 k/uL

Cannot have received: venetoclax (venetoclax)

Exception: prior venetoclax exposure ≤ 13 months and no known resistance to venetoclax

Prior venetoclax exposure > 13 months or known resistance to venetoclax

Cannot have received: targeted agent

Exception: ibrutinib, acalabrutinib, or zanubrutinib allowed

Treatment with targeted agents, investigational agents, therapeutic monoclonal antibodies, or cytotoxic chemotherapy within 5 half-lives or 2 weeks, whichever is shorter

Cannot have received: immunoconjugated antibody

Treatment with immunoconjugated antibody treatment within 10 weeks

Cannot have received: radiation therapy

Exception: palliative limited field radiation within 7 days prior to study enrollment allowed

Receipt of broad field radiation ( ≥ 30% of the bone marrow or whole brain radiotherapy) within 14 days or palliative limited field radiation within 7 days prior to study enrollment

Cannot have received: stem cell transplant

Exception: allogeneic SCT allowed if stable off all immunosuppression for at least 2 months prior to study screening

History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within 60 days

Cannot have received: CAR-T cell therapy

History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within 60 days