A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib or Venetoclax in Participants With R/R Hematologic Malignancies

Prior treatment

• Concurrent treatment or within 15 days of starting study treatment with strong CYP3A4 inhibitors
• Prior exposure to a CDK9 inhibitor
• Wait at least 5 half-lives of the agent or 14 days after their investigational or approved therapies before start of study treatment, whichever is shorter

Other illness

• Have active central nervous system involvement by malignancy, uncontrolled intercurrent illnesses, and active infections requiring systemic therapy
• Have undergone HSCT within the last 90 days or have graft versus host disease (GvHD) Grade \> 1 at study entry
• Have severe pulmonary disease with hypoxemia
• History of another malignancy except for adequately treated non-melanoma skin cancer or lentigo maligna, superficial bladder cancer, and carcinoma in situ of the cervix without evidence of disease, and asymptomatic prostate cancer without known metastatic disease and no requirement for therapy

Lab values

• Mean corrected QT interval of \> 470 msec following triplicate ECG measurement or history of long QT syndrome

Other

• T-Cell leukemias

• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
• Histologically or cytologically confirmed diagnosis of aggressive B-cell lymphoma subtypes, MCL, MZL, or CLL/SLL (including Richter's syndrome) based on local testing, or TCL (monotherapy only), AML, CMML, MDS, or MDS/MPN overlap syndrome that have relapsed or become refractory to or be ineligible for standard-of-care therapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of \< 2.
• Adequate organ function (hematology, renal, and hepatic)
• Echocardiogram (or multigated acquisition \[MUGA\] scan) indicating a left ventricular ejection fraction of ≥ 50%