The following criteria is provided for health care professionals.

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
• Left ventricular ejection fraction of ≥50%
• Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use a highly effective method of contraception during the trial
• Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ Grade 1)
• All patients on prior investigational agents must wait at least 5 half-lives of the agent in question, or 14 days, whichever is longer before study entry
• AML patients only: Pathologically confirmed diagnosis of AML as defined by the WHO Classification and patients with targeted mutations must have been treated with appropriate therapy for their disease
  • White blood cell count < 25 x 10^9/L. Hydrea or leukapheresis are permitted to meet this criterion.
• CMML patients only: intermediate-2 or high risk per CMML-specific prognostic scoring system (CPSS) or clinical/molecular CPSS (CPSS-mol) criteria. Must have failed prior therapy with a hypomethylating agent.
• MDS patients only: Intermediate, high, or very high risk by International Prognostic Scoring System-Revised [IPSS-R] criteria that is relapsed or refractory to approved therapies or MDS/MPN Overlap Syndrome (displaying both fibrosis and dysplastic features).
• NHL patients only: Histologically or cytologically confirmed NHL, including B- and T-cell lymphomas that is relapsed or refractory or intolerant to approved therapies. Must have one lesion that can be measured for response
• MM patients only: Measurable disease defined by one or more of the following: Serum M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours, Serum Free Light Chain (sFLC) > 10 mg/dL with normal serum FLC ratio. Presence of soft tissue plasmacytoma confirmed by imaging
• NHL and MM patients only: must have the following lab values within 14 days prior to study Day 1:
  • ANC ≥1.0 x 10^3 μL
  • Platelet count ≥50,000 μL

Exclusion Criteria:

• Known hypersensitivity to any of the components of PRT1419
• Female patients who are pregnant or lactating
• Mean QTcF interval of >480 msec
• History of heart failure, additional risk factors for arryhthmias or requiring concomitant medications that prolong the QT/QTc interval
• Hematopoietic stem-cell transplant < 90 days or have GVHD Grade >1 at study entry
• Uncontrolled intercurrent illnesses
• Treatment with strong inhibitors of CYP2C8 and/or P-glycoprotein for which there are no therapeutic substitutions
• Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
• HIV positive; known active hepatitis B or C
• Prior exposure to an MCL1 inhibitor
• History of another malignancy except:
  • Malignancy treated with curative intent with no known active disease for >2 years at study entry
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.