Title
Phase 1 Study of Venetoclax/Azacitidine or Venetoclax in Combination With Ziftomenib (Ko-539) Or Standard Induction Cytarabine/Daunorubicin (7+3) Chemotherapy in Combination With Ziftomenib for the Treatment of Patients With Acute Myeloid Leukemia

Description
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.

Objective
Primary Objectives:
-To determine the safety and tolerability of ziftomenib combined with SOC treatments in adults with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments in NPM1-m or KMT2A-r patients with R/R AML
-To determine the antileukemic activity of ziftomenib combined with SOC treatments in adults with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments in NPM1-m or KMT2A-r patients with R/R AML

Secondary Objectives:
- To evaluate survival, disease control outcomes and additional markers of antileukemic activity for ziftomenib combined with SOC treatments in adults with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments in NPM1-m or KMT2A-r patients with relapsed or refractory AML
- Characterize the pharmacokinetics of ziftomenib and metabolites when administered in combination with SOC treatments in adults with newly diagnosed NPM1-m or KMT2A-r AML and for ziftomenib combined with SOC treatments in NPM1-m or KMT2A-r patients with relapsed or
refractory AML
- To evaluate the potential drug interaction of ziftomenib on venetoclax (i.e., potential inhibition of CYP3A4 metabolism of venetoclax by ziftomenib)

Treatment Drug: Ziftomenib
Drug: Venetoclax
Drug: Azacitidine
Drug: Daunorubicin
Drug: Cytarabine

Key Eligibility Key Inclusion Criteria:

Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Adequate liver, renal, and cardiac function according to protocol defined criteria

A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health University Hospital