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Advanced Hematologic MalignancyPhase 1NCT04891757

FHD-286 as Monotherapy or Combination Therapy in Subjects With Advanced Hematologic Malignancies

A Phase 1 study testing FHD-286, Low Dose Cytarabine and Decitabine in people with Advanced Hematologic Malignancy and Relapsed Acute Myeloid Leukemia, run by Foghorn Therapeutics Inc. at 5 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This Phase 1, multicenter, open-label, dose escalation study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FHD-286 administered orally as monotherapy or combination therapy, in subjects with advanced hematologic malignancies. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
FHD-286, Low Dose Cytarabine and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
144 participants
Where
5 sitesUnited States
Study dates
14 Jun 2021to Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subject must be ≥16 years of age.
  • Subject must:
  • Have a confirmed diagnosis of R/R AML, R/R MDS, or R/R CMML not in blast crisis AND
  • Have received ≤4 prior lines of systemic anticancer therapy for their disease under study; subjects who have received >4 prior lines of systemic anticancer therapy for their disease under study must receive Sponsor approval. AND
  • Be an appropriate candidate for treatment with LDAC (Arm A) or decitabine (Arm B)
  • Subject or their parent or legal guardian (when applicable) must be able to understand and be willing to sign an informed consent and, when applicable, subject must sign an assent form.
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  • Subject must be willing and able to comply with scheduled study visits and treatment plans.
  • Subject must be willing to undergo all study procedures unless contraindicated due to medical risk.
  • Subject must have an ECOG PS of ≤2.
  • Subject must have a life expectancy of ≥3 months.
  • Subject must have adequate hepatic function.
  • Subject must have adequate renal function.
  • Subject must have a WBC count ≤20×109/L; treatment with a stable dose of hydroxyurea or other cytoreductive agent (eg, cytarabine) to achieve this count is allowed.
  • Subject must have adequate cardiovascular, respiratory, and immune system function.
  • Subject must agree to abide by dietary and other considerations required during the study.
  • Subject must meet timing requirements with respect to prior therapy and surgery
  • Toxicity related to prior therapy must have returned to Grade ≤2 by CTCAE by approximately 14 days before the start of study treatment or be deemed irreversible and stable by the Investigator. Exceptions include alopecia, neuropathy, appropriately controlled endocrine toxicities, and other well-controlled stable toxicities with discussion with the Sponsor.
  • Female subjects must be:
  • postmenopausal; or
  • permanently sterile, or, if sexually active with male partners, these partners must be azoospermic; or
  • nonpregnant, nonlactating, and, if sexually active with fertile male partners, having agreed to use a highly effective method of contraception
  • Male subjects must have documented azoospermia or, if fertile and sexually active, must agree to use a highly effective method of contraception with their partners of childbearing potential

Who cannot join

  • Subject is unable to provide informed consent and/or to follow protocol requirements.
  • Subject:
  • Has undergone chimeric antigen receptor T cell therapy or HSCT within 60 days of the first dose of study treatment OR
  • Has clinically significant GVHD
  • Subject has evidence (or suspicion) of extramedullary involvement, unless approved by Sponsor.
  • Subject has an immediately life-threatening, severe complication(s) of advanced myeloid malignancy, such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
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  • Subject has other malignancy that may interfere with the diagnosis and/or treatment of advanced hematologic malignancies.
  • Subject has active HBV or HCV infections; Subject has known positive HIV antibody results, or AIDS-related illness.
  • Subject has an active severe infection that requires anti-infective therapy or has an unexplained temperature of >38.5°C during screening visits or on their first day of study treatment.
  • Subject has an uncontrolled intercurrent illness.
  • Subject has QTcF >470 msec or other factors that increase the risk of QTc prolongation or arrhythmic events.
  • Subject has any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent/assent, cooperate, or participate in the study.
  • Subject has known allergies or hypersensitivities to:
  • All subjects: components of the FHD-286 formulation
  • Arm A: cytarabine or any of the excipients
  • Arm B: decitabine or any of the excipients
  • Subject is unable to tolerate the administration of oral medication or has GI dysfunction that would preclude adequate absorption, distribution, metabolism, or excretion of FHD-286.
  • Subject is receiving any other anticancer investigational agents. Investigational agents to treat non-cancer indications may be permitted with Sponsor approval.
  • Exclusion Criteria #14 was removed.
  • Subject is on medications classified as:
  • Strong CYP3A inhibitors [Exception: Triazole antifungal agents, including those classified as strong CYP3A inhibitors, are permitted.]
  • Strong CYP3A inducers
  • Sensitive CYP3A substrates with narrow TIs [Stable doses of immunosuppressant medications that are sensitive CYP3A4 substrates may be permitted with Sponsor approval.]
  • Subject is on medications with narrow TIs that are sensitive P-gp or BCRP substrates and are administered orally or on medications classified as strong inhibitors of P-gp or BCRP.
  • Administration of PPIs should be stopped or switched to another ARA 7 days before administration of FHD-286.
  • Subject is requiring clinically significant or increasing doses of systemic steroid therapy or any other systemic immunosuppressive medication. Local or targeted steroid and immunosuppressive therapies are acceptable. Appropriate steroid replacement to manage endocrine toxicities resulting from prior anticancer systemic therapy is permitted.
  • Subject has undergone any prior treatment with a BRG1/BRM inhibitor.
  • Subject is pregnant or breastfeeding or is planning to become pregnant within 1 year of the start of study treatment.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • City of Hope National Medical Center

    Duarte, California, 91010

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 1, Multicenter, Open-Label, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered FHD-286, as Monotherapy or Combination Therapy, in Subjects With Advanced Hematologic Malignancies

This Phase 1, multicenter, open-label, dose escalation study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FHD-286 administered orally as monotherapy or combination therapy, in subjects with advanced hematologic malignancies.

Read the detailed description

This study is primarily intended to evaluate the safety and tolerability of FHD-286 when administered orally as monotherapy or in combination with either LDAC or decitabine to subjects with R/R AML, R/R MDS, and R/R CMML not in blast crisis. In each arm of the study, successive cohorts of participants will receive increasing oral doses of FHD-286 as a single agent or in combination with LDAC or decitabine to determine the RP2D(s) in this population.

The data from this study in subjects with advanced hematologic malignancies, including safety, tolerability, PK/PD findings, and antitumor activity, will form the basis for subsequent clinical development of FHD-286.

Being tested
FHD-286, Low Dose Cytarabine, Decitabine
Keywords
AML, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, MDS, Relapsed Myelodysplastic Syndromes, Refractory Myelodysplastic Syndromes, Phase 1, FHD-286, Foghorn, CMML, Refractory Chronic Myelomonocytic Leukemia, Relapsed Chronic Myelomonocytic Leukemia
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FHD-286Drug

    FHD-286 administered orally

  • Low Dose CytarabineDrug

    Also called LDAC

    LDAC administered subcutaneously (SC)

  • DecitabineDrug

    Decitabine administered intravenously

Study groups in NCT04891757
Study groupRoleWhat they receive
FHD-286 MonotherapyExperimentalClosed to Enrollment
Receives: Drug: FHD-286
FHD-286 in Combination with LDACExperimentalFHD-286 administered orally + LDAC administered subcutaneously
Receives: Drug: FHD-286; Drug: Low Dose Cytarabine
FHD-286 in Combination with DecitabineExperimentalFHD-286 administered orally + decitabine administered intravenously (IV)
Receives: Drug: FHD-286; Drug: Decitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), AEs leading to discontinuation, and adverse events of special interest (AESIs); safety laboratory assessments

    Measured: Up to 18 months

Secondary outcomes (18)

  1. AML: Complete remission (CR) rate

    Measured: Up to 18 months

  2. AML: Duration of CR

    Measured: Up 18 months

  3. AML: CR + CR with partial hematologic recovery (CRh) rate

    Measured: Up 18 months

  4. AML: Duration of CR + CRh

    Measured: Up 18 months

  5. AML: Transfusion independence rate

    Measured: Up 18 months

  6. AML: Event free survival (EFS)

    Measured: Up 42 months

  7. AML: Overall survival (OS)

    Measured: Up to 42 months

  8. MDS: CR rate

    Measured: Up to 18 months

  9. MDS & CMML: Duration of CR

    Measured: Up to 18 months

  10. MDS & CMML: Partial remission (PR) rate

    Measured: Up to 18 months

  11. MDS & CMML: Duration of PR

    Measured: Up to 18 months

  12. MDS & CMML: CR + PR

    Measured: Up to 18 months

  13. MDS & CMML: Duration of CR + PR

    Measured: Up to 18 months

  14. MDS & CMML: Hematologic Improvement rate

    Measured: Up to 18 months

  15. MDS & CMML: EFS

    Measured: Up to 42 months

  16. MDS: OS

    Measured: Up to 42 months

  17. PK parameter: Area under the plasma concentration time curve (AUC)

    Measured: Day 1 and day 8 of cycle 1 (each cycle is 28 days)

  18. Plasma concentration vs. time profiles

    Measured: Day 1 and day 8 of cycle 1 (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2021
  2. Study start14 Jun 2021
  3. Primary completionSep 2025 (estimated)
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
144 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04891757
Sponsor's protocol ID
FHD-286-C-002
Status last verified
Mar 2025
First submitted
13 May 2021
Last updated
10 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • DiNardo CD, Fathi AT, Kishtagari A, Bhalla KN, Quintas-Cardama A, Reilly SA, Almon C, Patriquin C, Nabhan S, Healy K, Hickman D, Collins MP, Khalil A, Corrigan D, Zhao T, Piel J, Lyons K, Horrigan K, Schuck V, Martin P, Elliott G, Lahr DL, Bosinger M, D'Aco K, Smolen GA, Hentemann M, Loghavi S, Agresta S, Savona MR, Stein EM. A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies. Clin Cancer Res. 2025 Jun 13;31(12):2327-2338. doi: 10.1158/1078-0432.CCR-24-3790.

    PubMed 40238563

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing FHD-286, Low Dose Cytarabine and Decitabine in people with Advanced Hematologic Malignancy and Relapsed Acute Myeloid Leukemia, run by Foghorn Therapeutics Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), AEs leading to discontinuation, and adverse events of special interest (AESIs); safety laboratory assessments (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04891757, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.

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