Olutasidenib + Ziftomenib for Acute Myeloid Leukemia

Overseen By Courtney DiNardo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inducers

Disqualifiers: Acute promyelocytic leukemia, CNS leukemia, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for people with acute myeloid leukemia (AML), specifically those with NPM1 and IDH1 mutations. The main goal is to determine the optimal dose of two experimental drugs, ziftomenib and olutasidenib, and assess their effectiveness in controlling the disease. The trial will also evaluate the safety of these drugs when used together. This study targets individuals with AML that has recurred or is unresponsive to treatment, with these specific genetic mutations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that olutasidenib has a manageable safety profile for patients with mutated IDH1 acute myeloid leukemia (AML), meaning side effects were generally tolerable, even for those with extensive prior treatments. Similarly, research indicates that ziftomenib also has an encouraging safety profile when combined with other standard AML treatments, proving safe enough for continuous use. Although no specific data exists on the combined safety of olutasidenib and ziftomenib, both treatments have been well-tolerated individually in other studies. As this trial is in its early phase, determining the safest dose remains the main goal, with ongoing safety monitoring as a key component of the process. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Olutasidenib and Ziftomenib are unique because they target specific genetic mutations in acute myeloid leukemia (AML). Most treatments for AML, like chemotherapy, are broad and non-specific, affecting many types of cells. However, Olutasidenib specifically inhibits the mutated IDH1 enzyme, while Ziftomenib targets the NPM1 mutation. This precision in targeting potentially leads to more effective treatment with fewer side effects. Researchers are excited because this approach could offer a more personalized and potentially more successful treatment for patients with these specific genetic profiles.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that the drug olutasidenib yields promising results for treating acute myeloid leukemia (AML) in patients with certain gene mutations. In a study of 147 patients with these mutations, 51 achieved complete remission, with no signs of cancer detected. Another study reported a 35% remission rate with olutasidenib in patients whose cancer returned or did not respond to previous treatments. The drug ziftomenib has also proven effective, with complete remission rates between 23% and 25% in similar patient groups. This trial will evaluate the combination of olutasidenib and ziftomenib, which may help control AML in patients with specific gene mutations. ^{1 2 6 7 8}

Who Is on the Research Team?

Courtney DiNardo, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Inclusion Criteria

I am older than 18 years.

My AML has both IDH1 and NPM1 mutations.

I am able to care for myself and do light activities.

Exclusion Criteria

Subjects with white blood cell count > 20 x 10^9/L

I have acute promyelocytic leukemia with a t(15;17) chromosome change.

I have moderate to severe chronic graft-versus-host disease after a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Determine the safety, tolerability, and recommended phase 2 dose (RP2D) of ziftomenib and olutasidenib in 28-day cycles

28-day cycles

Monthly visits

Phase 1b Treatment

Evaluate the preliminary efficacy of the combination treatment in controlling the disease

28-day cycles

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olutasidenib
• Ziftomenib

How Is the Trial Designed?

Group I: Phase 1 Escalation and Phase 1b Expansion: Treatment with Ziftomenib + Olutasidenib Experimental Treatment 2 Interventions

Adult participants with relapsed/refractory NPM1m/ IDH1m AML will be enrolled. Treatment will consist of 28-day cycles of ziftomenib and olutasidenib given concomitantly. All participants will receive olutasidenib 150 mg orally twice daily (total 300 mg dose per day).

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07411586

Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 ...

The goal of Phase 1b is to learn if the recommended dose of ziftomenib and olutasidenib found in Phase 1 can help to control the disease. The ...

2.

ashpublications.org

ashpublications.org/bloodadvances/article/10/5/1537/557008/Outcomes-of-relapsed-or-refractory-acute-myeloid

Outcomes of relapsed or refractory acute myeloid leukemia ...

Key PointsAmong patients with R/R AML after MENINi treatment, outcomes are poor.Responses with further therapy are primarily seen with ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12619413/

Olutasidenib for mutated IDH1 acute myeloid leukemia - PMC

Among the 147 efficacy-evaluable patients, 51 achieved complete remission (CR) or CR with partial hematologic recovery (CRh), resulting in a CR/ ...

4.

onclive.com

onclive.com/view/clinical-efficacy-and-combination-therapy-development

Clinical Efficacy and Combination Therapy Development

KOMET-001 demonstrated 23% to 25% complete remission rates with 35% overall response rates, whereas AUGMENT-101 showed 23% complete remission ...

5.

ir.kuraoncology.com

ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-report-positive-combination-data

Press Release

100% of 1L NPM1-m and 96% of 1L KMT2A-r AML patients alive as of data cutoff with median follow-up of 31 and 19 weeks, respectively.

6.

kuraoncology.com

kuraoncology.com/perspectives/ziftomenib-combos-show-early-safety-activity-in-npm1-mutant-and-kmt2a-rearranged-aml/

Ziftomenib Combos Show Early Safety, Activity in NPM1- ...

“Ziftomenib demonstrates an encouraging safety and tolerability profile in combination with 7+3 and venetoclax/azacitidine, enabling continuous administration ...

7.

onclive.com

onclive.com/view/ziftomenib-combos-show-early-safety-activity-in-npm1-mutant-and-kmt2a-rearranged-aml

Ziftomenib Combos Show Early Safety, Activity in NPM1- ...

An acceptable safety profile and early evidence of clinical activity was observed with ziftomenib plus standard regimens in select patients with AML.

8.

clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT06001788

Ziftomenib Combinations in Patients With Relapsed/ ...

The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with ...