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Trial record 1 of 1 for:    NCT04879017
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FHD-286 in Subjects With Metastatic Uveal Melanoma

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ClinicalTrials.gov Identifier: NCT04879017
Recruitment Status : Recruiting
First Posted : May 10, 2021
Last Update Posted : August 2, 2022
Information provided by (Responsible Party):
Foghorn Therapeutics Inc.

Brief Summary:
This Phase 1, multicenter, open-label, dose escalation and expansion study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FHD-286 oral monotherapy in subjects with metastatic Uveal Melanoma (UM).

Condition or disease Intervention/treatment Phase
Metastatic Uveal Melanoma Drug: FHD-286 Phase 1

Detailed Description:

This study is an ascending multiple dose clinical trial with expansion arms. It is primarily intended to evaluate the safety and tolerability of FHD-286 when administered orally to subjects with metastatic UM. The Dose Escalation Phase will allow for the determination of the recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) in subjects with metastatic UM. This study will also evaluate the PK/PD profiles of multiple dose administration of FHD-286.

The Dose Expansion Phase will allow a more robust evaluation of the safety profile of FHD-286, including less frequent toxicities and an assessment of antitumor activity. The data from this study in subjects with metastatic UM, including safety, tolerability, PK/PD findings, and antitumor activity, will form the basis for subsequent clinical development of FHD-286.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open label single arm dose escalation and two-arm expansion study in patients with metastatic UM
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered FHD-286 in Subjects With Metastatic Uveal Melanoma
Actual Study Start Date : May 17, 2021
Estimated Primary Completion Date : August 29, 2023
Estimated Study Completion Date : August 29, 2025

Arm Intervention/treatment
Experimental: FHD-286 dose escalation and expansion
Up to approximately 100 patients will be enrolled in dose escalation and expansion
Drug: FHD-286
FHD-286 as a single agent

Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 31 months ]
    Dose escalation and expansion

  2. Incidence of adverse events (AEs), serious adverse events (SAEs) including changes in safety laboratory parameters and AEs leading to discontinuation [ Time Frame: Up to 31 months ]
    Dose escalation and expansion

  3. Incidence of dose limiting toxicities (DLTs) during cycle 1 (28 days) [ Time Frame: Cycle 1 (cycle length = 28 days) ]
    Dose escalation

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 30 months ]
    ORR is defined as the percentage of subjects with evidence of a complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

  2. Duration of Response (DOR) [ Time Frame: Up to 30 months ]
    DOR is defined as the time from first documented evidence of CR or PR until the earliest date of documented radiological progression per RECIST 1.1. or death due to any cause among subjects who achieved a CR or PR

  3. Time to Response (TTR) [ Time Frame: Up to 30 months ]
    TTR is defined as the period of time from the date of first study drug administration until the first objective documentation of a CR or PR per RECIST 1.1.

  4. Time to Progression (TTP) [ Time Frame: Up to 30 months ]
    TTP is defined as the time from the date of first study drug administration until the start of disease progression per RECIST Version 1.1.

  5. Progression Free Survival (PFS) [ Time Frame: Up to 54 months ]
    PFS defined as the time from first dose of study treatment until the first date of either objective disease progression per RECIST 1.1. or death due to any cause

  6. Overall Survival (OS) [ Time Frame: Up to 54 months ]
    OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death

  7. PK parameter: Area under the plasma concentration time curve (AUC) [ Time Frame: Cycle 1 (28 days) ]
    Characterization of the PK profile of FHD-286

  8. Plasma concentration vs. time profiles [ Time Frame: Cycle 1 (28 days) ]
    Plasma concentration of FHD-286 at the scheduled timepoints

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  • Male or female subjects ≥ 18 years of age
  • Subject must have a diagnosis of metastatic histologically or cytologically confirmed UM. If histologic or cytologic confirmation of the primary tumor is not available, clinical confirmation of a diagnosis of metastatic UM, as per standard practice for UM, by the treating investigator can be obtained, and fall into any of the following categories:

    1. Newly diagnosed subject who has not yet received liver-directed or systemic treatment
    2. Subjects ineligible for any available therapy likely to convey clinical benefit
    3. Subjects who have disease progression after treatment with available therapies and/or who is intolerant to those treatments.
  • Subjects must have measurable disease by RECIST v1.1, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥ 10 mm with calipers and/or CT scan. Measurable lesions cannot have undergone any local treatment (including liver-directed radio- or immune-therapies) or radiation nor can any local treatment or radiation involving measurable lesions be anticipated.
  • Willingness to provide newly obtained tumor tissue at baseline and on treatment unless contraindicated by medical risk in the opinion of the treating physician
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2. a.) Arm 2 (Dose Expansion Phase): Subjects enrolling in Arm 2 must have an ECOG PS of ≤ 3.

Key Exclusion Criteria:

  • Subjects who have other malignancy which may interfere with the diagnosis and/or treatment of metastatic UM.
  • Subject has thrombocytopenia (platelets < 50 × 109/L) or another major bleeding disorder/diathesis.

Note: Subjects with platelets < 50 × 109/L may be permitted to enroll only in Arm 2 of the Dose Expansion Phase at the discretion of the Investigator and the Sponsor.

  • Subjects with known CNS metastases are only permitted under the following conditions: Brain metastases must have been stable for approximately 2 months since completion of most recent CNS-directed intervention. Subject may be on corticosteroids so long as the dose is stable for approximately 14 days or decreasing at the time of study entry. Anti-epileptic therapy is allowed so long as medications are not otherwise excluded and seizures have been controlled for approximately 4 weeks since last anti-epileptic medication adjustment. Subjects with active brain metastases and/or leptomeningeal disease are excluded. Exceptions to this may be made on a case-by-case basis with approval of the Sponsor.

    1. Dose Escalation Phase: Subjects with known CNS metastases that meet the above conditions are permitted to enroll in dose escalation.
    2. Arm 1 (Dose Expansion Phase): Subjects with known or suspected CNS metastases are excluded from Arm 1.
    3. Arm 2 (Dose Expansion Phase): Subjects with CNS metastases that meet the above conditions are permitted to enroll in Arm 2.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections; subjects with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Subject has known positive human immunodeficiency virus (HIV) antibody results or acquired immunodeficiency syndrome (AIDS)-related illness; subjects with CD4+ T-cell counts greater than or equal to 350 cells/µL will be permitted, as will subjects who have not had an AIDS-related illness within the past 12 months
  • Subjects with an active infection cannot be enrolled until any required antibiotic and/or antifungal therapy has been completed and/or infection is determined to be controlled
  • Subjects who have an uncontrolled intercurrent illness.
  • Known and possible risk for QT prolongation.
  • Subject is on medications that are strong CYP3A inhibitors, are strong CYP3A inducers, or are sensitive CYP3A substrates with narrow TIs
  • Subject is on medications with narrow TIs that are sensitive P-gp or BCRP substrates and are administered orally such as digoxin
  • Subjects who require clinically significant or increasing doses of systemic steroid therapy or any other systemic immunosuppressive medication. The use of a stable dose of systemic steroids and/or immunosuppressive medication is permitted with Sponsor approval. Local or targeted steroid and immunosuppressive therapies (e.g. inhaled or topical steroids) are acceptable. Appropriate steroid replacement to manage endocrine toxicities resulting from prior systemic anticancer therapy is permitted.
  • Subjects have undergone any prior treatment with a BRG1/BRM inhibitor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04879017

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Contact: Foghorn Clinical Trials 1-888-615-1298 clinicaltrials@foghorntx.com

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United States, California
The Angeles Clinic and Research Institute Recruiting
Los Angeles, California, United States, 90025
Contact: Inder Mehmi, MD         
United States, Florida
University of Miami Health System, Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Leonel F Hernandez-Aya, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kamaneh Montazeri, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Elizabeth Buchbinder, MD         
United States, New York
Columbia University, Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Richard Carvajal, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Alexander Shoushtari, MD         
United States, Pennsylvania
Sidney Kimmel Cancer Center - Jefferson Health Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Marlana Orloff, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37205
Contact: Meredith McKean, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sapna Patel, MD         
Institute Curie Hospital Not yet recruiting
Paris, France
Contact: Sophie Piperno-Neumann, MD         
Leiden University Medical Center Not yet recruiting
Leiden, Netherlands
Principal Investigator: Ellen Kapitejin, MD         
Sponsors and Collaborators
Foghorn Therapeutics Inc.
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Study Director: Sarah Reilly, MD Foghorn Therapeutics
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Responsible Party: Foghorn Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04879017    
Other Study ID Numbers: FHD-286-C-001
First Posted: May 10, 2021    Key Record Dates
Last Update Posted: August 2, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Foghorn Therapeutics Inc.:
metastatic uveal melanoma
advanced uveal melanoma
phase 1
Additional relevant MeSH terms:
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Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases