PRT1419 as Monotherapy or in Combination With Azacitidine or Venetoclax in R/R Myeloid or B-cell Malignancies

Exclusion Criteria

• •Active inflammatory disorders of the gastrointestinal tract, a history of bariatric surgery or other disorders with the potential for GI malabsorption
• •Cardiac function compromise, as assessed by echocardiogram or protocol-specified biochemical markers of cardiac damage, or protocol-defined clinically significant heart disease
• •History of cerebrovascular accident or transient ischemic attack, within 6 months of screening. Participants with a history of pulmonary embolism must not be symptomatic at enrollment
• •Undergone hematopoietic stem-cell transplantation (HSCT) within the last 90 days or have graft-versus-host disease (GVHD) Grade \> 1 at study entry
• •Uncontrolled intercurrent illnesses, poorly controlled hypertension or dyslipidemias, Unstable central nervous system (CNS) metastases
• •Treatment with either OATP1B1, OATP1B3 substrates or strong inhibitors of CYP2C8, CYP3A4, and any medication contraindicated in combination with AZA or VEN
• •Prior exposure to an MCL-1 inhibitor
• •Within 5 half-lives or 14 days (whichever is longer) following the last systemic anti-cancer therapy
• •History of another malignancy except for:
• •1. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• •2. Adequately treated cervical or breast carcinoma in situ without evidence of disease
• •3. Asymptomatic prostate cancer without known metastatic disease and no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for \>1 year prior to enrollment
• •4. Other malignancy treated with curative intent with no known active disease for \> 2 years prior to enrollment