A Study of Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)

A Phase 2 Open-Label Study to Evaluate Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)

The purpose of this study is to evaluate the safety and efficacy of etavopivat (FT-4202) for the treatment of anemia in adult patients with very low risk, low risk, or intermediate risk MDS.

Study Overview

• Status: Terminated
• Conditions: Very Low Risk, Low Risk, or Intermediate Risk MDS Per IPSS-R
• Intervention / Treatment: Drug: Etavopivat

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • University of British Columbia - St. Paul's Hospital
• France
  • Paris, France
    • Hopital Saint Louis
  • Paris La Défense, France, 92936
    • Master centre for France
  • Pessac, France, 33600
    • Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-1
  • Nice
    • Route de Saint-Antoine, Nice, France, 06200
      • Nice University Hospital - Hôpital de l'Archet
• Germany
  • Heidelberg, Germany
    • Universitoetsklinikum Heidelberg
  • Mainz, Germany, 55124
    • Charité Universitätsmedizin Berlin
  • Mainz, Germany, 55124
    • Universitätsklinikum Leipzig, Klinik und Poliklinik
  • Münster, Germany
    • Universitaetsklinikum Muenster
  • Münster, Germany
    • Universitoetsklinikum Halle (Saale)
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics
    • Ocala, Florida, United States, 34474
      • Ocala Oncology
  • New Jersey
    • Plainsboro, New Jersey, United States, 08536
      • Cedars-Sinai Medical Center
    • Plainsboro, New Jersey, United States, 08536
      • Northwell Health
    • Plainsboro, New Jersey, United States, 08536
      • Northwestern Memorial Hospital
    • Plainsboro, New Jersey, United States, 08536
      • The Ohio State University Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

1. Patient has provided documented informed consent; the informed consent form (ICF) must be reviewed and signed by each patient prior to any study-related assessments/procedures being conducted.
2. Age ≥ 18 years at time of first dose.
3. Patients, if female and of childbearing potential, must agree to use acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug.

4. Documented diagnosis of idiopathic/de novo MDS according to World Health Organization (WHO) classification that meets the IPSS-R classification of very low, low, or intermediate risk disease, and:

   • < 5% blasts in bone marrow based on local pathology review
   • < Intermediate risk cytogenetic abnormalities per IPSS-R

5. Anemia defined as:

   • Non-transfusion dependent (NTD): Subjects with mean Hb concentration < 10.0 g/dL of 2 measurements (1 performed within 3 days prior to Day 1 and the other performed 7 to 28 days prior to Day 1, not influenced by RBC transfusion within 7 days of measurement) and < 3 RBC transfusions for anemia in the prior 16 weeks before Day 1 of etavopivat dosing

   OR

   • Transfusion dependent (TD): Subjects having received ≥ 3 units of RBCs for the treatment of anemia within 16 weeks prior to Day 1
6. Serum erythropoietin level > 200 U/L, OR, if ≤ 200 U/L, subject is non-responsive, refractory, or intolerant to erythropoiesis-stimulating agents, or erythropoiesis-stimulating agents are contraindicated or unavailable.
7. ECOG performance status of ≤ 2
8. Subject is non-responsive, refractory, or intolerant to luspatercept, or luspatercept is contraindicated or not indicated.
9. No alternative treatment options are available and/or appropriate for the subject, at the discretion of the investigator.
10. Patient is willing and able to adhere to the study visit schedule and other protocol requirements

EXCLUSION CRITERIA:

[MDS History]

1. MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality
2. Therapy-associated MDS (eg. t-MDS) that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases

3. Known history of acute myeloid leukemia (AML)

   [Medical Conditions]

4. Female who is breast feeding or pregnant
5. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
6. Absolute neutrophil count < 500/µL (0.5 x 10^9/L)
7. Platelet count < 50,000/µL (50 x 10^9/L) without transfusion support within 2 weeks

8. Hepatic dysfunction characterized by:

   • Alanine aminotransferase (ALT) > 5.0 × upper limit of normal (ULN)
   • Total bilirubin > 3.0 × ULN
   • History of cirrhosis
9. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory < 30 mL/min/1.73 m^2 ) or on chronic dialysis.

10. Patients with clinically significant and active bacterial, fungal, parasitic, or viral infection.

    • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay Screening/ enrollment until active therapy has been completed.
    • Patients with acute viral infections without available therapies (eg, coronavirus disease 2019 [COVID-19]) should delay Screening/ enrollment until the acute infection has resolved.

    Note: Infection prophylaxis is allowed.

11. Known human immunodeficiency virus (HIV) positivity
12. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive)
13. Active hepatitis C infection

14. History of malignancy, other than MDS, within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation.

    • Patients with malignancy considered surgically cured are eligible (eg, non-melanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast)
    • Patients with incidental histologic findings of prostate cancer (T1a or T1b) are eligible

15. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:

    • Unstable angina pectoris or myocardial infarction or elective coronary intervention
    • Heart disease, heart failure as classified by the New York Heart Association classification 3 or higher, or significant arrhythmia requiring treatment,
    • Pulmonary fibrosis or pulmonary hypertension which are clinically significant ie, ≥ Grade 3 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (or higher)
16. Uncontrolled hypertension, defined as repeated elevation of diastolic blood pressure ≥ 100 mmHg despite adequate treatment

17. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).

    [Prior/Concomitant Therapy]

18. Prior treatment with azacitidine (injectable or oral) or decitabine
19. Use of erythropoietin, other hematopoietic growth factor treatment or lenalidomide within 30 days of starting study treatment or anticipated need for such agents during the study.

20. Prior use of luspatercept:

    • NTD patients must not have received luspatercept within 30 days prior to Day 1 treatment
    • TD patients must not have received luspatercept within 16 weeks prior to Day 1 treatment
21. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP)3A4/5 (see Appendix F) within 2 weeks of starting study treatment or anticipated need for such agents during the study.
22. Prior allogeneic or autologous stem cell transplant

23. Initiation of a new chelation therapy within 3 months before the first dose of study treatment.

    [Prior/Concurrent Clinical Study Experience]

24. Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).

    [Other Exclusions]

25. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etavopivat 400 mg QD daily; Non-transfusion dependent (NTD), Low transfusion burden (LTB) , and High transfusion burden (HTB) patients	Drug: Etavopivat; 400 mg once daily; Other Names: FT-4202

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for >=8 Weeks Within 24 Weeks of Etavopivat Treatment	This outcome measure reported on the combined incidence of NTD, LTB and HTB in terms of (HI-E) response for >=8 weeks duration in participants with myelodysplastic syndromes (MDS) within 24 weeks. The participants were allocated to the following arms which were defined as: 1) NTD: >=1.5 grams per deciliter (g/dL) increase in haemoglobin (Hb) from baseline maintained >=8 consecutive weeks and no transfusion of RBC units for anemia over a continuous 8-week treatment period; 2) LTB: absence of any transfusion for >=8 consecutive weeks; and 3) HTB: reduction by >=50 percent (%) of RBC units for >=8 consecutive weeks.	From Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hematologic Improvement-Erythroid (HI-E) Response for =>8 Weeks Within 16 and 48 Weeks of Etavopivat	This outcome measure focused on the combined incidence of NTD, LTB and HTB participants, evaluating HI-E lasting =>8 weeks in individuals with MDS within 16 weeks and 48 weeks. Participant's response were defined as follows: 1) NTD: an increase of =>1.5 g/dL in Hb maintained for =>8 consecutive weeks without any RBC transfusions for anemia; 2) LTB: no transfusions over =>8 consecutive weeks; and 3) HTB: a reduction of =>50% in RBC units for =>8 consecutive weeks.	48 weeks
Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for =>16 Weeks Within 24 and 48 Weeks of Etavopivat	This outcome measure focused on the combined incidence of NDT, LTB and HTB participants, evaluating HI-E response lasting =>16 weeks in individuals with MDS within 24 weeks and 48 weeks. Participant's response were defined as follows: 1) NTD: an increase of =>1.5 g/dL in Hb maintained for =>16 consecutive weeks without any RBC transfusions for anemia; 2) LTB: no transfusions over =>16 consecutive weeks; and 3) HTB: a reduction of =>50% in RBC units for =>16 consecutive weeks.	48 weeks
Number of All Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Related to Etavopivat	This outcome measures the total number of AEs and SAEs in participants, including AEs related to etavopivat. AEs are any unfavorable medical occurrences in participants taking the medicinal product, regardless of causality. They include new or worsening symptoms, abnormal lab findings, and exacerbations of existing conditions, documented from the first dose through 28 days after the last dose. SAEs are severe AEs that result in death, are life-threatening, require hospitalization, lead to significant disability, or involve congenital anomalies. Important medical events posing risks to the participants are also classified as SAEs. Treatment Emergent Adverse Events (TEAEs) are AEs occurring after treatment initiation, aiding in the safety assessment of etavopivat. TEAEs will be considered drug-related if assessed by the Investigator as possibly related or related, or if relationship is missing.	From baseline up to 48 weeks
Number of Premature Discontinuations, Dose Interruptions, and Dose Reductions	The outcome measures the total number of premature discontinuations, dose interruptions and dose reductions. Premature discontinuation was defined as any discontinuation prior to week 48. A dose interruption is a temporary halt in treatment due to an AE, while a dose reduction involves lowering the dosage of the drug when AEs occur. If a participant tolerates a reduced dose for 14 days, a rechallenge with the original dose may occur after a clinic visit, but any new Grade 3 or higher AEs require treatment discontinuation and consultation with the Global Medical Monitor before resuming.	Within 48 weeks
Overall Response Rate	The Overall Response Rate (ORR) is defined as the percentage of participants who achieve a predefined level of response according to the 2006 International Working Group (IWG) criteria, assessed at each scheduled evaluation.	Up to 48 weeks
Duration of Response	This outcome measure reported duration of response which was defined as duration of response will be summarized with quantiles based on product limit estimates (ie, Kaplan-Meier). Duration of response is defined as the time from date of first known incidence of a 2006 IWG criteria response to the most recent date that the 2006 IWG (International Working Group) criteria is not met following the initial response. If the participant has met IWG criteria throughout the period following the initial response, the participant will be censored at the latest date of end of study, loss to follow-up, or death.	Up to 48 weeks
Reduction in RBC Transfusions for >=8 Weeks in Participants With LTB or HTB at Study Entry	This outcome measure reports reduction in RBC transfusion by 8-week interval in participants with LTB and HTB.	Up to 48 weeks
Percent Change From Baseline in RBC Transfusion Independence for =>8 Weeks in Participants With LTB or HTB at Study Entry	This outcome measure is percent change in RBC transfusion by 8-week interval in participants with LTB and HTB. Percent reduction from baseline in RBC transfusion burden is defined as -100×(Total RBC Units Transfused During Interval)/(Baseline RBC Units Transfused Per 8 Weeks).	Up to 48 weeks
Change From Baseline in Neutrophils and/or Platelets Counts	This outcome measure reports the change from baseline in neutrophils and/or platelets counts from baseline to week 48	Baseline (week 0), week 48
Decrease in Ferritin and Transferrin Saturation (TSAT)	This outcome measure were to report decrease in ferritin and TSAT from baseline to Week 48.	Up to 48 weeks
Decrease in Iron Chelation Therapy	This outcome measure were to report decrease of Iron chelation therapy and will be recorded at Screening and on an ongoing basis throughout the study.	up to 48 weeks
Overall Survival	Overall survival is defined as the time from first dose to date of death. If the participant was alive at last contact, the end date will be censored at the latest of either end of study, loss to follow-up, or study discontinuation.	Within 48 weeks
Etavopivat Plasma Concentrations	This outcome measure reported Etavopivat plasma concentrations in order to assess the PK properties of etavopivat in participants with MDS. PK parameters included but not limited to were: Time to maximum observed plasma concentration, area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last), from time zero to infinity (AUC0-inf), for a dosing interval (AUCtau/AUC0-24).) However due to early termination of the study, the PK parameters were not assessed and only the plasma concentrations could be assessed.	Weeks 1 and 4 pre-dose, post-dose 1, 2, 4, 6 hours.Week 2 and EOT (week 48):pre-dose, post-dose 1, 2 hours
RBC 2,3-diphosphoglycerate (2,3-DPG) and Adenosine Triphosphate (ATP) Levels Over Time	Etavopivat plasma concentrations were collected in order to assess the pharmacodynamic (PD) properties of etavopivat in participants with MDS.	Within 48 weeks

Collaborators and Investigators

• Sponsor: Forma Therapeutics, Inc.
• Investigators: Study Director: Clinical Transparency (dept. 2834), MD, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Actual): July 15, 2024
• Study Completion (Actual): July 15, 2024

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Estimated): October 22, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Anemia; MDS; Myelodysplastic Syndromes; Pyruvate Kinase; Transfusion dependent; Activator; FT-4202; Etavopivat; IPSS-R very low risk; IPSS-R low risk; IPSS-R intermediate risk; ESA refractory; ESA intolerant; Luspatercept refractory; Luspatercept intolerant
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Anemia
• Other Study ID Numbers: 4202-ONC-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No