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

NCT04891757 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: FHD-286-C-002
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Advanced Hematologic Malignancy; Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Relapsed Myelodysplastic Syndromes; Refractory Myelodysplastic Syndromes; Relapsed Chronic Myelomonocytic Leukemia; Refractory Chronic Myelomonocytic Leukemia

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

Outcome Measures

Primary Outcomes (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

  Up to 18 months

Secondary Outcomes (18)

• AML: Complete remission (CR) rate

  Up to 18 months

• AML: Duration of CR

  Up 18 months

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

  Up 18 months

• AML: Duration of CR + CRh

  Up 18 months

• AML: Transfusion independence rate

  Up 18 months

Study Arms (3)

FHD-286 Monotherapy

EXPERIMENTAL

Closed to Enrollment

Drug: FHD-286

FHD-286 in Combination with LDAC

EXPERIMENTAL

FHD-286 administered orally + LDAC administered subcutaneously

Drug: FHD-286; Drug: Low Dose Cytarabine

FHD-286 in Combination with Decitabine

EXPERIMENTAL

FHD-286 administered orally + decitabine administered intravenously (IV)

Drug: FHD-286; Drug: Decitabine

Interventions

FHD-286 DRUG

FHD-286 administered orally

FHD-286 Monotherapy; FHD-286 in Combination with Decitabine; FHD-286 in Combination with LDAC

Low Dose Cytarabine DRUG

LDAC administered subcutaneously (SC)

Also known as: LDAC

FHD-286 in Combination with LDAC

Decitabine DRUG

Decitabine administered intravenously

FHD-286 in Combination with Decitabine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Foghorn Therapeutics Inc.: lead

Study Sites (5)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 40238563 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Cytarabine; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Azacitidine; Aza Compounds; Organic Chemicals; Ribonucleosides

Study Officials

• Sarah Reilly, MD

  Foghorn Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 18, 2021
• Study Start: June 14, 2021
• Primary Completion: September 1, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-03

Locations

US (5)