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
- Conditions
- Metastatic Uveal MelanomaUM10027476
- Registration Number
- NL-OMON53846
- Lead Sponsor
- Foghorn Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
1. Subject must be >= 18 years of age.
2. Subject 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:
• Newly diagnosed subject who has not yet received liver-directed or systemic
treatment
• Subject ineligible for any available therapy likely to convey clinical benefit
• Subject who has disease progression after treatment with available therapies
and/or who is intolerant to those treatments.
Note: Inclusion criterion 15 provides timing requirements for prior therapy.
3. 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.
4. Subject must be able to understand and be willing to sign an informed
consent.
5. Subject must be willing and able to comply with scheduled study visits and
treatment plans.
6. Subject must be willing to undergo all study procedures (fresh biopsies at
baseline, at least 1 additional biopsy on-treatment, and 1 EOT biopsy [unless
contraindicated due to medical risk]; archival biopsies of sufficient sample
size collected within 6 months of first dose and subsequent to other prior
therapies will be accepted as a substitute for a fresh baseline biopsy; other
exceptions to this are at the discretion of the Sponsor), laboratory testing,
and imaging every 8 weeks for 48 weeks and 12 weeks thereafter until
relapse/progression, start of alternate anticancer therapy, or withdrawal from
the study, independent of dose delays, interruptions, or reductions.
7. Subject must have adequate venous access for blood collection.
8. Subject must have an ECOG PS of <= 2.
• Arm 2 (Dose Expansion Phase): Subjects enrolling in Arm 2 must have an ECOG
PS of <= 3.
9. Subject must have a life expectancy of >= 3 months.
• Arm 2 (Dose Expansion Phase): Subjects enrolling in Arm 2 must have a life
expectancy of >= 2 months.
10. Subject must have adequate hepatic function as evidenced by:
• Serum total bilirubin <= 1.5 × upper limit of normal (ULN) (<= 3.0 × ULN for
subjects with Gilbert*s syndrome)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <= 3.0 × ULN
(<= 5.0 × ULN if liver metastases are present)
• Prothrombin time (PT) <= 1.5 × ULN or international normalized ratio (INR) <=
1.4
• Activated partial thromboplastin time (aPTT) <= 1.5 x ULN
Note: Anticoagulation therapy is permitted as long as coagulation parameters
are within therapeutic range.
• No known portal vein thrombosis
Note: Subjects with organ function outside the parameters outlined in the above
inclusion criterion may be perm
1. Subject is unable to provide informed consent and/or to follow protocol
requirements.
2. 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.
3. Subject has active brain metastases and/or leptomeningeal disease. Subjects
with known central nervous system (CNS) metastases are only permitted under the
following conditions; exceptions may be made on a case-by-case basis with
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 (see exclusion criteria 13 and 14) 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.
4. Subject has other malignancy which may interfere with the diagnosis and/or
treatment of metastatic UM.
5. Subject has 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 >= 350 cells/µL will be permitted, as
will subjects who have not had an AIDS-related illness within the past 12
months.
6. Subject has an active infection. Subject is permitted to enroll once any
required antibiotic and/or antifungal therapy has been completed and/or
infection is determined to be controlled.
7. Subject has an uncontrolled intercurrent illness.
8. Subject has corrected QT interval (QTc) using Fridericia*s formula (QTcF) >
470 msecs or other factors that increase the risk of QTc prolongation or
arrhythmic events (eg, heart failure, hypokalemia, family history of long QT
interval syndrome) including heart failure that meets New York Heart
Association (NYHA) class III and IV definitions (see Appendix 15.2). Subjects
with bundle branch block and a prolonged QTc should be reviewed by the Sponsor
for potential inclusion.
9. Subject has any other medical or psychological condition, deemed by the
Investigator to be likely to interfere with a subject*s ability to sign
informed consent, cooperate, or participate in the study.
10. Subject has known hypersensitivities to components of the FHD-286
formulation.
11. Subject is unable to tolerate the administration of oral medication or has
gastrointestinal (GI) dysfunction that would preclude adequate absorption,
distribution, metabolism, or excretion of study drug.
12. Subject is participating in any other clinical tri
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Incidence of treatment-emergent adverse events (TEAEs), AEs, dose-limiting<br /><br>toxicities (DLTs), serious AEs (SAEs), and AEs leading to discontinuation;<br /><br>safety laboratory assessments</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Objective Response Rate (ORR)<br /><br>• Duration of Response (DOR)<br /><br>• Time to Response (TTR)<br /><br>• Time to Progression (TTP)<br /><br>• Progression Free Survival (PFS)<br /><br>• Overall Survival (OS)<br /><br>• PK parameter: Area under the plasma concentration time curve (AUC)<br /><br>• Plasma concentration vs. time profiles</p><br>