A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients With AML

• Status: Not yet recruiting
• Trial end date: 2027-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kura Oncology, Inc.
• Treatments: Azacitidine; Cytarabine; Daunorubicin; Venetoclax

Criteria

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

Key Exclusion Criteria:

• Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia

• Known history of BCR-ABL alteration

• Advanced malignant hepatic tumor [for patients receiving ven/aza combination]

• Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery

• Active central nervous system (CNS) involvement by AML.

• Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea and/or leukapheresis are permitted to meet this criterion

• Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia

• Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection

• For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome

• For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational < 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug

• Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol

• Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) >480 ms on triplicate ECGs

• Uncontrolled infection

• Women who are pregnant or lactating

• An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing