Trial Title:
Study of REM-422 in Patients With AML or Higher Risk MDS
NCT ID:
NCT06297941
Condition:
Myelodysplastic Syndromes
Higher Risk Myelodysplastic Syndromes
Acute Myeloid Leukemia
Acute Myeloid Leukemia Refractory
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
REM-422
Description:
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
Arm group label:
REM-422
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
Detailed description:
This is a Phase 1, open-label, non-randomized, multicenter study investigating REM-422, a
potent, selective, and oral small molecule mRNA degrader that reduces expression of the
MYB transcription factor for patients with higher risk MDS or relapsed/refractory AML.
This study includes a Dose Escalation Phase and a Dose Expansion Phase. The purpose of
the Dose Escalation Phase is to determine the maximum tolerated dose (MTD) and/or
recommended Phase 2 dose (RP2D) of REM-422 in patients with higher risk MDS or
relapsed/refractory AML. The purpose of Dose Expansion is to further evaluate the safety
and anti-tumor activity of the RP2D carried forward from Dose Escalation.
Participation in this study will continue until disease progression, therapy intolerance,
or participant withdrawal.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Be able to provide informed consent.
2. Be 18 or older at the time of informed consent.
3. Disease criteria:
Histologically confirmed diagnosis of either:
1. 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.
2. 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).
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Has agreed to undergo serial blood and bone marrow sampling.
6. 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.
7. Toxicities from prior therapy must be either stable or recovered to ≤ Grade 1.
8. Participants must be able to swallow and retain oral medications.
9. Oxygen saturation > 92% on room air or up to 2 L/min supplemental oxygen by nasal
cannula with ≤ Grade 1 dyspnea.
10. People of childbearing potential (POCBP) must have a negative serum beta-human
chorionic gonadotropin test result.
11. 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.
12. 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.
13. Adequate organ function and laboratory parameters
Exclusion Criteria:
1. Active central nervous system (CNS) leukemia or a confirmed diagnosis of CNS
leukemia.
2. 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).
3. Has immediate, life-threatening, severe complications of leukemia, such as
uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated
intravascular coagulation.
4. Known hypersensitivity or contraindication to any component of REM-422 or to drugs
chemically related to REM-422 or its excipients.
5. 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).
6. Evidence of active HIV infection.
7. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
8. Primary immunodeficiency.
9. 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.
10. Live vaccine ≤ 6 weeks prior to the start of REM-422.
11. Use of strong CYP3A inhibitors (except azole antifungals) or CYP3A inducers
12. 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.
13. Currently pregnant, have intentions to become pregnant during the study duration, or
are currently lactating.
14. Has dysphagia, short-gut syndrome, gastroparesis, or any other condition that limits
the ingestion or gastrointestinal absorption of orally administered drugs.
15. Current use of prohibited medication ≤ 1 week before starting REM-422.
16. Clinically significant cardiovascular disease:
17. Has undergone major surgery (opening a mesenchymal barrier such as the pleural
cavity, peritoneum, or meninges or surgical procedures requiring general anesthesia)
< 4 weeks prior to enrollment.
18. History of organ transplant that requires use of immunosuppressive agents.
19. History or current autoimmune disease requiring systemic treatment (eg, Crohn's
disease, ulcerative colitis, rheumatoid arthritis, systemic lupus).
20. Radiation therapy ≤ 7 days prior to the start of REM-422.
21. Concurrent or previous other malignancy ≤ 2 years of enrollment, except curatively
treated malignancies including basal or squamous cell skin cancer, breast cancer,
prostate intraepithelial neoplasm, and carcinoma in situ of the cervix.
22. Receiving any other investigational treatment for any indication ≤ 3 weeks prior to
enrollment.
23. Unwillingness or inability to follow protocol requirements.
24. Any condition that, in the opinion of the Investigator, would interfere with
evaluation of REM-422 or interpretation of the participant's safety or study
results.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Anthony S Stein, MD
Email:
Principal Investigator
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Onyee Chan, MD
Email:
Principal Investigator
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Amir Fathi, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Eytan M Stein, MD
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Courtney D DiNardo, MD
Email:
Principal Investigator
Start date:
April 26, 2024
Completion date:
June 15, 2027
Lead sponsor:
Agency:
Remix Therapeutics
Agency class:
Industry
Source:
Remix Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06297941