FHD-286 in Subjects With Metastatic Uveal Melanoma

NCT04879017 | Terminated Phase 1 FDA Drug

• 1 other identifier: FHD-286-C-001
• Study Type: interventional
• Target: 76
• Locations: 3 countries
• Sites: 11

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).

Conditions

Metastatic Uveal Melanoma

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-emergent adverse events (TEAEs)

  Dose escalation and expansion

  Up to 31 months

• Incidence of adverse events (AEs), serious adverse events (SAEs) including changes in safety laboratory parameters and AEs leading to discontinuation

  Dose escalation and expansion

  Up to 31 months

• Incidence of dose limiting toxicities (DLTs) during cycle 1 (28 days)

  Dose escalation

  Cycle 1 (cycle length = 28 days)

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  Up to 30 months

• Duration of Response (DOR)

  Up to 30 months

• Time to Response (TTR)

  Up to 30 months

• Time to Progression (TTP)

  Up to 30 months

• Progression Free Survival (PFS)

  Up to 54 months

Study Arms (1)

FHD-286 dose escalation and expansion

EXPERIMENTAL

Up to approximately 125 patients will be enrolled in dose escalation and expansion

Drug: FHD-286

Interventions

FHD-286 DRUG

FHD-286 as a single agent

FHD-286 dose escalation and expansion

Eligibility Criteria

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

You may qualify if:

• 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:
• Newly diagnosed subject who has not yet received liver-directed or systemic treatment
• Subjects ineligible for any available therapy likely to convey clinical benefit
• Subjects who have disease progression after treatment with available therapies and/or who is intolerant to those treatments.
• Subject 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, unless there has been interim progression of that lesion, nor can any local treatment or radiation involving measurable lesions be anticipated.
• Note: A malignant lymph node must be ≥ 15 mm on the short axis when assessed by CT scan to be considered pathologically enlarged and measurable.
• 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.

You may not qualify if:

• 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.
• Subject has active brain metastases and/or leptomeningeal disease. Subjects with known CNS metastases are only permitted under the following conditions; exceptions may be made on a case-by-case basis with the approval of the Sponsor: 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.
• Dose Escalation Phase: Subjects with known CNS metastases that meet the above conditions are permitted to enroll in dose escalation.
• Arm 1 (Dose Expansion Phase): Subjects with known or suspected CNS metastases are excluded from Arm 1.
• 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 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 have undergone any prior treatment with a BRG1/BRM inhibitor.

Sponsors & Collaborators

• Foghorn Therapeutics Inc.: lead

Study Sites (11)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

University of Miami Health System, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sidney Kimmel Cancer Center - Jefferson Health

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37205, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institute Curie Hospital

Paris, France

Location

Leiden University Medical Center

Leiden, Netherlands

Location

MeSH Terms

Conditions

Uveal Melanoma

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Sarah Reilly, MD

  Foghorn Therapeutics

  STUDY DIRECTOR

Study Design

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

Model Details: Open label single arm dose escalation and two-arm expansion study in patients with metastatic UM

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: May 10, 2021
• Study Start: May 11, 2021
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); FR (1); NL (1)