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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04879017
Other study ID # FHD-286-C-001
Secondary ID
Status Terminated
Phase Phase 1
First received
Last updated
Start date May 11, 2021
Est. completion date November 30, 2023

Study information

Verified date April 2024
Source Foghorn Therapeutics Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Terminated
Enrollment 76
Est. completion date November 30, 2023
Est. primary completion date November 30, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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. - 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. 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. - 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. 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 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. See exclusion criterion 3 for exceptions regarding steroid therapy for subjects with CNS metastases. See exclusion criterion 13 for exclusions regarding medications that are strong CYP3A inhibitors, strong CYP3A inducers, or sensitive CYP3A substrates with narrow TIs. - Subjects have undergone any prior treatment with a BRG1/BRM inhibitor.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
FHD-286
FHD-286 as a single agent

Locations

Country Name City State
France Institute Curie Hospital Paris
Netherlands Leiden University Medical Center Leiden
United States Dana Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States MD Anderson Cancer Center Houston Texas
United States The Angeles Clinic and Research Institute Los Angeles California
United States University of Miami Health System, Sylvester Comprehensive Cancer Center Miami Florida
United States Sarah Cannon Research Institute Nashville Tennessee
United States Columbia University, Herbert Irving Comprehensive Cancer Center New York New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States Sidney Kimmel Cancer Center - Jefferson Health Philadelphia Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Foghorn Therapeutics Inc.

Countries where clinical trial is conducted

United States,  France,  Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of treatment-emergent adverse events (TEAEs) Dose escalation and expansion Up to 31 months
Primary 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
Primary Incidence of dose limiting toxicities (DLTs) during cycle 1 (28 days) Dose escalation Cycle 1 (cycle length = 28 days)
Secondary Objective Response Rate (ORR) 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. Up to 30 months
Secondary Duration of Response (DOR) 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 Up to 30 months
Secondary Time to Response (TTR) 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. Up to 30 months
Secondary Time to Progression (TTP) 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. Up to 30 months
Secondary Progression Free Survival (PFS) 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 Up to 54 months
Secondary Overall Survival (OS) OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death Up to 54 months
Secondary PK parameter: Area under the plasma concentration time curve (AUC) Characterization of the PK profile of FHD-286 Cycle 1 (28 days)
Secondary Plasma concentration vs. time profiles Plasma concentration of FHD-286 at the scheduled timepoints Cycle 1 (28 days)
See also
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Recruiting NCT04728633 - Transarterial Chemoembolization for the Treatment of Uveal Melanoma With Liver Metastases Phase 2
Recruiting NCT05987332 - IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma Phase 2/Phase 3
Completed NCT01551459 - A Phase II Study of Sunitinib Versus Dacarbazine in the Treatment of Patients With Metastatic Uveal Melanoma Phase 2
Active, not recruiting NCT00986661 - A Study to Assess PV-10 Chemoablation of Cancer of the Liver Phase 1
Completed NCT01585194 - Nivolumab and Ipilimumab in Treating Patients With Metastatic Uveal Melanoma Phase 2
Withdrawn NCT01328106 - Efficacy and Safety Study of GSK1120212, a MEK Inhibitor, in Subjects With Uveal Melanoma Phase 2
Recruiting NCT05075993 - Study of LVGN3616 and LVGN6051±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors Phase 1
Active, not recruiting NCT04552223 - Nivolumab Plus Relatlimab in Patients With Metastatic Uveal Melanoma Phase 2
Recruiting NCT05607095 - Pilot Trial of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Patients With Metastatic Uveal Melanoma Phase 1
Active, not recruiting NCT01587352 - Vorinostat in Treating Patients With Metastatic Melanoma of the Eye Phase 2
Active, not recruiting NCT03025256 - Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease Phase 1
Active, not recruiting NCT03472586 - Ipilimumab and Nivolumab With Immunoembolization in Treating Participants With Metastatic Uveal Melanoma in the Liver Phase 2
Terminated NCT01814046 - Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Ocular Melanoma Phase 2
Recruiting NCT03947385 - Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions Phase 1/Phase 2
Active, not recruiting NCT03865212 - Modified Virus VSV-IFNbetaTYRP1 in Treating Patients With Stage III-IV Melanoma Phase 1
Active, not recruiting NCT05022901 - An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma Phase 3
Recruiting NCT05282901 - Efficacy and Safety of Pembrolizumab in Combination With Lenvatinib in Metastatic Uveal MElanoma Patients (PLUME) Phase 2
Recruiting NCT05415072 - A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas Phase 1/Phase 2
Active, not recruiting NCT04720417 - Defactinib and VS-6766 for the Treatment of Patients With Metastatic Uveal Melanoma Phase 2