FHD-286 in Subjects With Metastatic Uveal Melanoma

• Status: Recruiting
• Trial end date: 2025-08-29
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Foghorn Therapeutics Inc.
• Collaborator: Syneos Health

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 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 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; stable doses of steroids are allowed for control of chronic symptoms, as long as the dose is stable for approximately 2 weeks before study start. 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.