This is a single-arm, open-label, Phase II study to evaluate the safety and efficacy of venetoclax combined with pirtobrutinib (VEN-P) in participants with symptomatic Waldenström Macroglobulinemia (WM) with previously treated disease. Pirtobrutinib blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps cells live and grow. Venetoclax blocks BCL-2, a protein essential for WM cells' survival.~The U.S. Food and Drug Administration (FDA) has not approved pirtobrutinib for Waldenström Macroglobulinemia (WM), but it has been approved for other uses.~The FDA has not approved venetoclax for Waldenström Macroglobulinemia (WM), but it has been approved for other uses.~The FDA has not approved the combination of pirtobrutinib and venetoclax as a treatment for any disease.~Study procedures include screening for eligibility, treatment visits, CT scans, blood tests, and bone marrow aspirates and biopsies.~Participants will receive study treatment for up to 2 years and will be followed for up to 4 years or until they start a new therapy.~It is expected that about 42 people will take part in this research study.~Eli Lilly supports this research study by providing study drug pirtobrutinib and funding.
This study is being done to examine the safety and effectiveness of pirtobrutinib combined with venetoclax as a possible treatment for participants with Waldenström Macroglobulinemia (WM).~The names of the study drugs involved in this study are:~Pirtobrutinib (a Noncovalent Bruton Tyrosine Kinase (BTK) inhibitor)~Venetoclax (a BCL2 inhibitor)