Study of REM-422 in Patients With AML or Higher Risk MDS

NCT06297941 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: REM-422-102
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 9

Brief Summary

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 AML

Conditions

Myelodysplastic Syndromes; Higher Risk Myelodysplastic Syndromes; Acute Myeloid Leukemia; Acute Myeloid Leukemia Refractory

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of Treatment Emergent Adverse Events (TEAEs)

  Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and number of participants with Dose Limiting Toxicities will be assessed to determine Safety and Tolerability of REM-422 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.

  24 months

• Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

  Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and the number of participants with Dose Limiting Toxicities will be assessed from the date of first dose of REM-422 until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months

  Assessed at the end of Cycle 1 (each cycle is 28 days) for each participant for approximately 24 months

Secondary Outcomes (14)

• AML: Rate of Complete Response (remission) (CR)

  24 months

• AML: Rate of CR with partial hematologic recovery (CRh)

  24 months

• AML: Duration of CR

  24 months

• AML: Duration of CRh

  24 months

• AML: Overall response rate (ORR) (CR + CRh + CRi + PR) with incomplete hematologic recovery [CRi] + partial response [PR]) per modified IWG response criteria 2003 based on Investigator assessment

  24 months

Study Arms (1)

REM-422

EXPERIMENTAL

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

Drug: REM-422

Interventions

REM-422 DRUG

REM-422 is a first in class, small molecule mRNA inhibitor that reduces expression of the MYB transcription factor REM-422 will be administered orally once daily

REM-422

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to provide informed consent.
• Be 18 or older at the time of informed consent.
• Disease criteria:
• Histologically confirmed diagnosis of either:
• R/R AML, defined as relapse after transplantation, second or later relapse, refractory to initial induction or reinduction treatment or to initial treatment with hypomethylating (HMA)-based combinations, relapse after initial treatment, or otherwise considered relapsed or refractory in the opinion of the Investigator.
• High-risk and very-high-risk (VHR) MDS (higher-risk) per the International Prognostic Scoring System-Revised (IPSS-R) and/or International Prognostic Scoring System-Molecular (IPSS-M).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has agreed to undergo serial blood and bone marrow sampling.
• Participants must have completed systemic non-investigational therapy at least 14 days prior to initiating REM-422. Hydroxyurea is permissible for controlling peripheral leukemic blasts prior to enrollment and for up to 28 days following initiation of REM-422.
• Toxicities from prior therapy must be either stable or recovered to ≤ Grade 1.
• Participants must be able to swallow and retain oral medications.
• Oxygen saturation \> 92% on room air or up to 2 L/min supplemental oxygen by nasal cannula with ≤ Grade 1 dyspnea.
• People of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.
• POCBP must agree to use acceptable, effective methods of contraception and not donate ova from screening until 6 months after discontinuation of REM-422. Women who have undergone surgical or ablative sterilization or who have been postmenopausal for ≥ 2 years are not considered to be of childbearing potential.
• Men must agree to use acceptable, effective methods of contraception and must agree not to donate sperm from the start of receiving REM-422 until 6 months after discontinuation of REM-422.

You may not qualify if:

• Active central nervous system (CNS) leukemia or a confirmed diagnosis of CNS leukemia.
• Has undergone hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of REM-422 or is receiving immunosuppressive therapy post HSCT at the time of screening, or has GVHD requiring systemic treatment (topical steroids for ongoing skin GVHD is permitted).
• Has immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
• Known hypersensitivity or contraindication to any component of REM-422 or to drugs chemically related to REM-422 or its excipients.
• Clinically significant active infection. Note: Patients with simple urinary tract infection or uncomplicated bacterial pharyngitis responding to active treatment are permitted. Note: Patients receiving intravenous (IV) antibiotics ≤ 7 days prior to enrollment are excluded (prophylactic antibiotics, antivirals, or antifungals are permitted).
• Evidence of active HIV infection.
• Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Primary immunodeficiency.
• Current or expected need for daily systemic corticosteroid therapy ≥ 10 mg of prednisone equivalent.
• Note: Patients who are receiving topical or inhaled corticosteroids with minimal systemic absorption are eligible for enrollment and may continue with minimal corticosteroid use as long as they are on a stable dose.
• Live vaccine ≤ 6 weeks prior to the start of REM-422.
• Use of strong CYP3A inhibitors (except azole antifungals) or CYP3A inducers
• Drugs that reduce gastric acidity, such as H2-receptor antagonists (eg, ranitidine, famotidine) and proton pump inhibitors (eg, omeprazole, esomeprazole) within 7 days prior to the initiation of REM-422 administration or during the study.
• Currently pregnant, have intentions to become pregnant during the study duration, or are currently lactating.
• Has dysphagia, short-gut syndrome, gastroparesis, or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs.

Sponsors & Collaborators

• Remix Therapeutics: lead

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Memorial Sloan Kettering

New York, New York, 10065, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Centre Hospitalier Universitaire (CHU) de Bordeaux

Bordeaux, France

RECRUITING

AP-HP - Hôpital Saint-Louis

Paris, France

RECRUITING

IUCT-Oncopole

Toulouse, France

RECRUITING

Institut de Cancerologie Gustave-Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Christopher Bowden, MD

  Remix Therapeutics

  STUDY CHAIR

Central Study Contacts

Remix Therapeutics

CONTACT

781-827-0902; ClinicalTrials@remixtx.com

Rosalie Jiang

CONTACT

781-584-9390; rjiang@remixtx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: March 7, 2024
• Study Start: April 26, 2024
• Primary Completion: March 15, 2026
• Study Completion (Estimated): June 15, 2027
• Last Updated: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); US (5)