Clinical Trials /

FHD-286 in Subjects With Metastatic Uveal Melanoma

NCT04879017

Description:

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).

Related Conditions:
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: FHD-286 in Subjects With Metastatic Uveal Melanoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: FHD-286-C-001
  • NCT ID: NCT04879017

Conditions

  • Metastatic Uveal Melanoma

Interventions

DrugSynonymsArms
FHD-286FHD-286 dose escalation and expansion

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
FHD-286 dose escalation and expansionExperimentalUp to approximately 100 patients will be enrolled in dose escalation and expansion
  • FHD-286

Eligibility Criteria

        Key Inclusion Criteria:

          -  Male or female subjects ≥ 18 years of age

          -  Subjects must have a diagnosis of metastatic histologically or cytologically confirmed
             UM. If histologic or cytologic confirmation of the 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 one lesion
             that can be accurately measured in at least one 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.

          -  Subjects who have 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 Medical Monitor.

          -  Subjects with known central nervous system (CNS) metastases are only permitted under
             the following conditions: Brain metastases must have been stable for at least 2 months
             since completion of most recent CNS-directed intervention. Subject may be on
             corticosteroids so long as the dose is stable 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 at least 4 weeks since last
             anti-epileptic medication adjustment. Subjects with active brain metastases and/or
             leptomeningeal disease are excluded.

               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.

          -  Subjects who are receiving treatment with medications that cannot be discontinued
             prior to study entry and that are considered to be any of the following:

               1. known to be strong Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors, are
                  strong CYP3A inducers, or are sensitive CYP3A substrates with narrow therapeutic
                  indices (TIs)

               2. known to have narrow TIs that are sensitive P glycoprotein (P gp) or breast
                  cancer resistance protein (BCRP) substrates and are administered orally, such as
                  digoxin known to be acid-reducing agents (ARAs) such as histamine H2-receptor
                  antagonists (H2 blockers), and proton pump inhibitors (PPIs). Antacids are
                  acceptable when administered in a staggered dosing manner with FHD-286

          -  Subjects who are receiving systemic steroid therapy or any other systemic
             immunosuppressive medication. Local steroid therapies (inhaled or topical steroids)
             are acceptable. Appropriate steroid replacement to manage endocrine toxicities
             resulting from prior systemic anticancer therapy is permitted. See exclusion criterion
             3 for exceptions regarding steroid therapy for subjects with CNS metastases.

          -  Subjects have undergone any prior treatment with a BRG1/BRM inhibitor.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events (TEAEs)
Time Frame:Up to 31 months
Safety Issue:
Description:Dose escalation and expansion

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 30 months
Safety Issue:
Description:ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.
Measure:Duration of Response (DOR)
Time Frame:Up to 30 months
Safety Issue:
Description: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 confirmed CR or PR
Measure:Time to Response (TTR)
Time Frame:Up to 30 months
Safety Issue:
Description:TTR is defined as the period of time from the date of first study drug administration until the first objective documentation of response per RECIST 1.1.
Measure:Time to Progression (TTP)
Time Frame:Up to 30 months
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS)
Time Frame:Up to 54 months
Safety Issue:
Description: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
Measure:Overall Survival (OS)
Time Frame:Up to 54 months
Safety Issue:
Description:OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death
Measure:PK parameter: Area under the plasma concentration time curve (AUC)
Time Frame:Day 1 and day 8 of cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Characterization of the PK profile of FHD-286
Measure:Plasma concentration vs. time profiles
Time Frame:Day 1 and day 8 of cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Plasma concentration of FHD-286 at the scheduled timepoints

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Foghorn Therapeutics Inc.

Trial Keywords

  • UM
  • metastatic uveal melanoma
  • advanced uveal melanoma
  • phase 1
  • FHD-286
  • Foghorn

Last Updated

May 10, 2021