Table of contents

• Trial overview
• Adult relapsed or refractory AML studies
• Children’s study with chemotherapy
• Phase 3 study in newly diagnosed AML
• Key outcomes being measured
• Who may join these trials

Trial overview

The clinical trial program for Ziftomenib is focused on acute leukemia, especially acute myeloid leukemia (AML), and also includes some related blood cancers.^[1][2][3] The studies are testing Ziftomenib in different settings: as a first-in-human treatment in adults with relapsed or refractory disease, in children with relapsed or refractory acute leukemia, and in adults with newly diagnosed AML that has specific genetic changes.^[1][2][3]

These trials are interventional studies, which means the researchers give a treatment and then measure the results.^[1][2][3] The phases range from Phase 1 to Phase 3, so the program includes early testing for safety and dose, as well as larger studies that look at treatment benefit.^[1][2][3]

Adult relapsed or refractory AML studies

NCT04067336 is a Phase 1/2 study in adults with relapsed or refractory AML.^[1] “Relapsed” means the cancer came back after treatment, and “refractory” means it did not respond well to treatment.^[1] This study is authorised and plans to enroll 205 people.^[1]

The early part of this trial looks for the maximum tolerated dose, which is the highest dose that can be given without too many serious problems, and the recommended phase 2 dose, which is the dose chosen for later studies.^[1] Later parts of the study look at safety, tolerability, and signs that the treatment may be helping.^[1]

This trial also includes sub-studies. One sub-study measures pharmacokinetics, which means how Ziftomenib and its breakdown products move through the body.^[1] Other sub-studies look at activity in adults with KMT2A-rearranged acute lymphoblastic leukemia and in AML with mutations linked to MEIS1 overexpression.^[1]

Children’s study with chemotherapy

NCT06376162 is a Phase 1 study in children with relapsed or refractory acute leukemia.^[2] The study includes acute myeloid leukemia, mixed phenotype acute leukemia, and acute lymphocytic leukemia.^[2] It is authorised and plans to enroll 20 participants.^[2]

This study tests Ziftomenib together with chemotherapy, including fludarabine and cytarabine, and also intrathecal Solu-Cortef in one part of the treatment plan.^[2] Intrathecal means the medicine is given into the fluid around the brain and spinal cord.^[2] The main goal is to find the recommended phase 2 dose based on dose-limiting toxicities and pharmacokinetic results.^[2]

Dose-limiting toxicities are side effects that are serious enough to limit how much treatment can be given.^[2] The study also includes children with specific genetic types of acute leukemia, including KMT2A-rearranged, NUP98-rearranged, and NPM1-mutated disease.^[2]

Phase 3 study in newly diagnosed AML

NCT07007312 is a Phase 3 study for adults with newly diagnosed AML that has either an NPM1 mutation or a KMT2A rearrangement.^[3] It is authorised and has the largest planned enrollment in this set of trials, with 1,320 participants.^[3]

This study compares Ziftomenib with standard treatment approaches in two settings.^[3] In the nonintensive therapy study, it is tested with venetoclax and azacitidine, and the main outcome is overall survival.^[3] In the intensive therapy study, it is tested with standard 7+3 chemotherapy, and the main outcome is event-free survival.^[3]

Overall survival means how long people live after treatment starts, and event-free survival means how long people stay free from treatment failure, relapse, or death.^[3] This Phase 3 study is important because it is designed to test whether adding Ziftomenib can improve major patient outcomes in newly diagnosed AML with these genetic changes.^[3]

Key outcomes being measured

The trial program measures several important outcomes across different phases.^[1][2][3] Early studies focus on safety, tolerability, dose selection, and pharmacokinetics.^[1][2]

In the adult Phase 1/2 study, researchers also track complete remission and complete remission with partial hematologic recovery, which are signs that the blood cancer has responded to treatment.^[1] In the Phase 3 study, the main outcomes are overall survival in the nonintensive arm and event-free survival in the intensive arm.^[3]

In the children’s Phase 1 study, the main goal is to choose the best dose for later testing using safety and drug exposure data.^[2] Drug exposure means how much of the drug gets into the body and how long it stays there.^[2]

Who may join these trials

The adult studies are for people with AML, especially those with relapsed or refractory disease or newly diagnosed disease with NPM1 mutation or KMT2A rearrangement.^{[1][3] The child study is for children with relapsed or refractory acute leukemia, including AML, mixed phenotype acute leukemia, and acute lymphocytic leukemia.[2]}

Some parts of the adult Phase 1/2 study also include people with KMT2A-rearranged acute lymphoblastic leukemia and AML with MEIS1-related mutations.^[1] Because each trial has its own rules, the exact group that can join depends on the study and the disease features being tested.^[1][2][3]