Metastatic Uveal MelanomaPhase 1NCT04879017
FHD-286 in Subjects With Metastatic Uveal Melanoma
A Phase 1 study testing FHD-286 in people with Metastatic Uveal Melanoma, run by Foghorn Therapeutics Inc. at 11 sites in 3 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Uveal Melanoma
- What is being tested?
- FHD-286
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 11 May 2021to 30 Nov 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States9 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
MD Anderson Cancer Center
Houston, Texas, 77030
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
University of Miami Health System, Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Sarah Cannon Research Institute
Nashville, Tennessee, 37205
Columbia University, Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Sidney Kimmel Cancer Center - Jefferson Health
Philadelphia, Pennsylvania, 19107
About this study
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
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).
Read the 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.
- Conditions
- Metastatic Uveal Melanoma
- Being tested
- FHD-286
- Keywords
- UM, metastatic uveal melanoma, advanced uveal melanoma, phase 1, FHD-286, Foghorn
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FHD-286Drug
FHD-286 as a single agent
| Study group | Role | What they receive |
|---|---|---|
| FHD-286 dose escalation and expansion | Experimental | Up to approximately 125 patients will be enrolled in dose escalation and expansion Receives: Drug: FHD-286 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events (TEAEs)
Dose escalation and expansion
Measured: 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
Measured: Up to 31 months
Incidence of dose limiting toxicities (DLTs) during cycle 1 (28 days)
Dose escalation
Measured: Cycle 1 (cycle length = 28 days)
Secondary outcomes (8)
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.
Measured: Up to 30 months
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
Measured: Up to 30 months
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.
Measured: Up to 30 months
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.
Measured: Up to 30 months
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
Measured: Up to 54 months
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
Measured: Up to 54 months
PK parameter: Area under the plasma concentration time curve (AUC)
Characterization of the PK profile of FHD-286
Measured: Cycle 1 (28 days)
Plasma concentration vs. time profiles
Plasma concentration of FHD-286 at the scheduled timepoints
Measured: Cycle 1 (28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2021
- Study start11 May 2021
- Primary completion30 Nov 2023
- Study completion30 Nov 2023
Why it stopped: Sponsor terminated the study for business reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Uveal MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label single arm dose escalation and two-arm expansion study in patients with metastatic UM
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Foghorn Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sarah Reilly, MD, Study director, Foghorn Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04879017
- Sponsor's protocol ID
- FHD-286-C-001
- Status last verified
- Apr 2024
- First submitted
- 28 Apr 2021
- Last updated
- 25 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04879017
- Acronym / sponsor ID
- FHD-286-C-001
- Conditions
- Metastatic Uveal Melanoma
- Keywords
- UM, metastatic uveal melanoma, advanced uveal melanoma, phase 1, FHD-286, Foghorn
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor terminated the study for business reasons.
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Foghorn Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 11 May 2021 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 Nov 2023 (actual)
- First posted
- 10 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label single arm dose escalation and two-arm expansion study in patients with metastatic UM
| Arm | Type | Receives |
|---|---|---|
| FHD-286 dose escalation and expansion | Experimental | Drug: FHD-286Up to approximately 125 patients will be enrolled in dose escalation and expansion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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
Key exclusion criteria (15 listed)
- 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.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FHD-286FHD-286 as a single agent | Drug | FHD-286 dose escalation and expansion |
Primary outcome
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: Up to 31 months
Dose escalation and expansion
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
Incidence of dose limiting toxicities (DLTs) during cycle 1 (28 days)
Time frame: Cycle 1 (cycle length = 28 days)
Dose escalation
8 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to 30 months
Duration of Response (DOR)
Time frame: Up to 30 months
Time to Response (TTR)
Time frame: Up to 30 months
Time to Progression (TTP)
Time frame: Up to 30 months
Progression Free Survival (PFS)
Time frame: Up to 54 months
Overall Survival (OS)
Time frame: Up to 54 months
PK parameter: Area under the plasma concentration time curve (AUC)
Time frame: Cycle 1 (28 days)
Plasma concentration vs. time profiles
Time frame: Cycle 1 (28 days)
Results and safety
The study was stopped early (reason given: Sponsor terminated the study for business reasons.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarah Reilly, MD study director
Foghorn Therapeutics
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FHD-286 in people with Metastatic Uveal Melanoma, run by Foghorn Therapeutics Inc. at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor terminated the study for business reasons.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events (TEAEs) (time frame: Up to 31 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2024.