REM-422 for Acute Myeloid Leukemia and Higher Risk MDS

Recruiting at 9 trial locations

Overseen By Remix Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Remix Therapeutics

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: CNS leukemia, Active infection, HIV, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and cancer-fighting effects of a new drug, REM-422, for individuals with Acute Myeloid Leukemia (AML) that hasn't responded to treatment, or a high-risk form of Myelodysplastic Syndromes (MDS). The study aims to determine the optimal dose of REM-422 by gradually increasing the dose for participants. Candidates may qualify if they have AML that recurred or didn't respond to treatment, or if they have been diagnosed with high-risk MDS. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

The trial requires that you stop systemic non-investigational therapy at least 14 days before starting REM-422. However, you can continue using hydroxyurea to control leukemic blasts before and up to 28 days after starting REM-422. Some medications, like strong CYP3A inhibitors and drugs that reduce stomach acid, must be stopped 7 days before starting the trial.

Is there any evidence suggesting that REM-422 is likely to be safe for humans?

Research has shown that REM-422 is being tested for safety in people with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS). As REM-422 remains in the early testing stages, detailed safety information from human trials is not yet widely available. The current phase focuses on determining the optimal dose that patients can tolerate. Researchers closely monitor for any side effects or adverse reactions.

Early-phase trials like this are specifically designed to assess safety. The treatment's effects on participants are carefully observed, and adjustments are made to minimize risks. Participants receive the treatment under strict supervision, ensuring that any side effects are managed promptly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

REM-422 is unique because it's an oral capsule designed to target acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). Unlike traditional chemotherapy, which often requires complex intravenous administration, REM-422's oral delivery method offers more convenience and potentially fewer hospital visits. Researchers are particularly excited about its dose-escalation approach, which aims to identify the maximum tolerated dose, offering a tailored treatment strategy that could enhance efficacy and safety. This targeted approach may provide a gentler alternative to the more aggressive traditional therapies, which can be harsh on the body.

What evidence suggests that REM-422 might be an effective treatment for acute myeloid leukemia and higher risk MDS?

Research has shown that REM-422, the investigational treatment in this trial, offers a promising new option for acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). REM-422 breaks down a specific type of mRNA, a molecule involved in protein production linked to cancer cell growth. This mRNA affects the MYB gene, often active in these cancers. Although data remains limited, early studies suggest that targeting this gene could inhibit cancer cell growth. While still under investigation in this trial, its unique mechanism provides researchers with hope for its potential effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Christopher Bowden, MD

Principal Investigator

Remix Therapeutics

Are You a Good Fit for This Trial?

This trial is for individuals with higher risk Myelodysplastic Syndrome (MDS) or relapsed/refractory Acute Myeloid Leukemia (AML). Specific eligibility criteria are not provided, but typically include factors like age, disease stage, and overall health.

Inclusion Criteria

I agree to use effective birth control methods.

My organs are functioning well according to recent tests.

People of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result

Exclusion Criteria

Receiving any other investigational treatment for any indication ≤ 3 weeks prior to enrollment

I currently have a serious infection.

I am receiving treatment for an autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of REM-422 to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

Until MTD/RP2D is determined

Dose Expansion

Participants receive REM-422 at the identified RP2D to further evaluate safety and anti-tumor activity

Until disease progression, therapy intolerance, or participant withdrawal

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• REM-422

Trial Overview The study is testing the safety and effectiveness of REM-422, a new treatment designed to target MYB mRNA in patients with high-risk MDS or AML that has come back or hasn't responded to other treatments.

How Is the Trial Designed?

Group I: REM-422 Experimental Treatment 1 Intervention

Dose Escalation: Participants will receive escalating doses of REM-422 to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)-422, oral capsule administered once daily Dose Expansion: Participants will receive REM-422 at the identified RP2D Treatment will continue until disease progression, therapy intolerance, or participant withdrawal Safety evaluation will continue until 30 days of last administration of REM-422

REM-422 is already approved in United States for the following indications:

Approved in United States as REM-422 for:

• Adenoid Cystic Carcinoma (ACC)
• Acute Myeloid Leukemia (AML)

Who Is Running the Clinical Trial?

Remix Therapeutics

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

MYB is identified as a promising drug target for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC), with recent studies showing that it can be effectively inhibited by low molecular weight compounds.

The proteasome inhibitor oprozomib was found to significantly inhibit MYB activity and reduce the proliferation of AML and ACC cells, suggesting a novel therapeutic approach by targeting MYB through proteasome inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteasome inhibitors suppress MYB oncogenic activity in a p300-dependent manner. Yusenko, MV., Biyanee, A., Andersson, MK., et al.[2022]

RUVBL2 is crucial for the function of the c-MYB transcription factor in acute myeloid leukemia (AML), as it represses genes associated with myeloid differentiation, allowing leukemia cells to self-renew.

Inhibiting RUVBL2 led to increased c-MYB activity, resulting in apoptosis of AML cells and significantly slowing disease progression in mouse models, while sparing normal blood cell development, suggesting a targeted therapeutic strategy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The AAA+ATPase RUVBL2 is essential for the oncogenic function of c-MYB in acute myeloid leukemia. Armenteros-Monterroso, E., Zhao, L., Gasparoli, L., et al.[2022]

Mebendazole has been identified as a novel therapeutic agent for acute myeloid leukemia (AML) by targeting the c-MYB transcription factor, which is crucial for AML development, particularly in cases with MLL-rearrangements.

In laboratory studies, mebendazole effectively inhibited the growth of AML cells without affecting normal blood cells, and it demonstrated the ability to impair AML progression in mouse models, suggesting it could be a safe treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting acute myeloid leukemia by drug-induced c-MYB degradation. Walf-Vorderwülbecke, V., Pearce, K., Brooks, T., et al.[2019]

The Myb protein is linked to various cancers, particularly acute myeloid leukemia (AML), but its exact role in these diseases is still not fully understood despite extensive research over the past 30 years.

Recent studies have identified Myb's transcriptional targets, suggesting that targeting Myb and its co-regulators could lead to new therapeutic strategies for treating hematopoietic malignancies, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role and potential for therapeutic targeting of MYB in leukemia. Pattabiraman, DR., Gonda, TJ.[2013]

The study identifies several protein kinase inhibitors, including bosutinib, as potential MYB-inhibitory agents, which could be repurposed to target malignancies like acute myeloid leukemia (AML).

These inhibitors disrupt MYB's ability to activate genes by interfering with its interaction with the coactivator p300, leading to increased cell death in AML cells, indicating a promising mechanism for treating MYB-dependent cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Src-Family Protein Kinase Inhibitors Suppress MYB Activity in a p300-Dependent Manner. Biyanee, A., Yusenko, MV., Klempnauer, KH.[2022]

The transcription factor MYB is crucial for the self-renewal of acute myeloid leukemia (AML) cells, indicating its importance in the progression of the disease.

C/EBPβ has been identified as a key collaborator with MYB and p300 in sustaining leukemic cells, suggesting it could be a promising therapeutic target for AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C/EBPβ cooperates with MYB to maintain the oncogenic program of AML cells. Klempnauer, KH.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06297941

Study of REM-422 in Patients With AML or Higher Risk MDS The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with Higher Risk MDS and relapsed/refractory ...

2. remixtx.com remixtx.com/rem-422/

REM-422 REM-422 is a first-in-class orally available, small molecule mRNA degrader that targets the pre-mRNA of MYB, a previously undruggable transcription factor known ...

3. mskcc.org mskcc.org/cancer-care/clinical-trials/24-102

A Phase 1 Study of REM-422 in People With Acute Myeloid ... In this study, researchers want to find the best dose of REM-422 to treat leukemia or myelodysplastic syndrome (MDS).

4. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-1051.html

A phase 1, multicenter, open-label study of REM-422, an ... The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with Higher Risk MDS and ...

5. trialx.com trialx.com/clinical-trials/listings/290712/study-of-rem-422-in-patients-with-aml-or-higher-risk-mds/

Study of REM-422 in Patients With AML or Higher Risk MDS Overview. The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with Higher Risk ...