FHD-609 in Subjects With Advanced Synovial Sarcoma

  • STATUS
    Recruiting
  • End date
    May 31, 2025
  • participants needed
    70
  • sponsor
    Foghorn Therapeutics Inc.
Updated on 19 September 2021

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-609 given intravenously in subjects with advanced synovial sarcoma.

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-609 when administered intravenously to subjects with advanced synovial sarcoma. 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 advanced synovial sarcoma. This study will also evaluate the PK/PD profiles of multiple dose administration of FHD-609.

The Dose Expansion Phase will allow a more robust evaluation of the safety profile of FHD-609, including less frequent toxicities and an assessment of anti-tumor activity. The data from this study in subjects with advanced synovial sarcoma, including safety, tolerability, PK/PD findings, and anti-tumor activity, will form the basis for subsequent clinical development of FHD-609

Details
Condition Advanced Synovial Sarcoma
Treatment FHD-609
Clinical Study IdentifierNCT04965753
SponsorFoghorn Therapeutics Inc.
Last Modified on19 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Subject must be 18 or 16 years of age with a minimum body weight of 50 kg
Subject must have a diagnosis of SS, defined by the presence of the SS18-SSX rearrangement, as confirmed by the Investigator (evidence from the diagnostic pathology of prior biopsy must be available). Subject must have advanced SS, which for the purposes of this study, is defined as any of the following
Metastatic
Local (primary or recurrent), unresectable (with Investigator and Medical Monitor approval)
Subject must have been treated with 4 regimens of systemic chemotherapies
Subjects who have undergone > 4 regimens of systemic chemotherapy may be
permitted with Medical Monitor approval. Subjects must have
Demonstrated progression of disease on their most recent therapy or
Discontinued their most recent therapy due to the potential for cumulative toxicity, intolerability or lack of continued clinical benefit, in the opinion of the Investigator
Eligible subjects with progression of disease on their most recent therapy may
enroll in the Dose Escalation Phase and in Arm 1 of the Dose Expansion Phase
Eligible subjects with responsive and/or stable disease on their most recent
therapy may enroll in the Dose Escalation Phase and in Arm 2 of the Dose
Expansion Phase
Note: Inclusion criterion 15 provides timing requirements for prior therapy
\. Subject 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 or radiation nor can any
local treatment or radiation involving measurable lesions be anticipated
\. Subject or his/her parent or legal guardian (when applicable) must be able
to understand and be willing to sign an informed consent and, when applicable
subject must sign assent form
\. Subject must be willing and able to comply with scheduled study visits and
treatment plans
\. Subject must be willing to undergo all study procedures (biopsies at
baseline, at least 1 on-treatment and at EOT [unless contraindicated due to
medical risk; other exceptions to this are at the discretion of the Sponsor's
Medical Monitor]), laboratory testing, and imaging approximately every 8 (or
) weeks independent of dose delays, interruptions, and/or reductions
\. Subject must have an ECOG PS of 2
Arm 2 (Dose Expansion Phase): Subject must have an ECOG PS of 3
\. Subject must have a life expectancy of 3 months
Arm 2 (Dose Expansion Phase): Subject must have a life expectancy of 2 months
\. Subject must have adequate venous access for IV drug administration and
blood collection
\. Subject must have adequate cardiac function as evidenced by
LVEF of 40% by ECHO. Other methods of evaluating LVEF may be performed according to institutional practice
Corrected QT interval (QTc) using Fridericia's formula (QTcF) < 470 msec 11. 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)
Alkaline phosphatase (ALP) 3.0 ULN ( 5.0 ULN if liver metastases are present and/or known bone disease is present)
No known portal vein thrombosis 12. Subject must have adequate renal function as evidenced by
Glomerular filtration rate (GFR) 50 mL/min (based on a contemporary, widely
accepted, and clinically applicable equation that estimates glomerular
filtration rate or a measure of glomerular filtration rate (e.g. Chronic
Kidney Disease Epidemiology Collaboration CKD-EPI)
\. Subject must have adequate hematologic function as evidenced by
Hemoglobin 8 g/dL (Red blood cell [RBC] transfusions to achieve this level will be permitted up to 7 days prior to start of study drug and complete blood count [CBC] criteria for eligibility are confirmed within 24 hours of first study dose.)
White blood cells (WBCs) 2.0 109/L
Absolute neutrophil count (ANC) 1.0 109/L
Platelets > 50 109/L (Transfusions to achieve this level will be allowed up to 72 hours prior to start of study drug.) 14. Subject must have adequate coagulation function as evidenced by
International normalized ratio (INR) 1.5 or prothrombin time (PT) 1.5 ULN and
partial thromboplastin time (PTT) 1.5 ULN if not receiving anticoagulation
therapy
Note: For subjects on anticoagulants, exceptions to these parameters are
allowed if they are within the intended or expected range for their
therapeutic use. Participants must have no history of clinically significant
active bleeding (within 14 days of first dose of study drug) or pathological
condition that carries high risk of bleeding (for example, tumor involving
major vessels or known esophageal varices)
\. Timing requirements with respect to prior therapy and surgery are as
follows
At least 2 weeks or at least 5 half-lives, whichever is shorter, must have elapsed since administration of the last dose of any prior anticancer therapy (including investigational agents)
weeks must have elapsed since the last major surgery, laparoscopic procedure, or significant traumatic injury. Note: Central line placement, subcutaneous port placement, core biopsy, fine needle aspiration, and bone marrow biopsy/aspiration are not considered major surgeries
weeks must have elapsed since the last radiotherapy. Palliative radiation therapy is allowed so long as it does not involve the target lesion(s). 16. Toxicity related to prior therapy must have returned to Grade 1 by CTCAE at least 14 days prior to study start. Exceptions include Grade 2 alopecia and other Grade 2 toxicities determined to be stable and irreversible by the Investigator with approval of the Medical Monitor. 17. Female subjects must be
Postmenopausal, defined as at least 12 months post-cessation of menses (without an alternative medical cause); or
Permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation or having a male partner with vasectomy or having a female partner as affirmed by the subject; or
Nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception (ie, hormonal contraceptives associated with inhibition of ovulation or intrauterine device [IUD], or intrauterine hormone-releasing system [IUS], or sexual abstinence) from Screening Visit until 90 days after final dose of study drug. 18. Male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential (ie, hormonal contraceptives associated with the inhibition of ovulation or IUD, or IUS, or sexual abstinence) from Screening until 90 days after final dose of study drug. Male subjects must agree to refrain from donating sperm during this time period

Exclusion Criteria

Subject (or his/her parent or legal guardian, when applicable) is unable to provide informed consent (or assent, when applicable) and/or to follow protocol requirements
Subject has other malignancy which may interfere with the diagnosis and/or treatment of SS and/or interpretation of outcome results
Subject has an active severe infection requiring systemic therapy. Subject is permitted to enroll once any required antibiotic and/or antifungal therapy has been completed and/or infection is determined to be controlled
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 human immunodeficiency virus (HIV) antibody results or acquired immunodeficiency syndrome (AIDS)-related illness; subjects with CD4+ T-cell counts 350 cells/L will be permitted, as will subjects who have not had an AIDS-related illness within the past 12 months
Subject has an uncontrolled concurrent medical disease and/or psychiatric illness/social situation that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol
Subject is receiving systemic steroid therapy for acute illness (stable doses for controlled chronic disease are permitted) or any other systemic immunosuppressive medication. Local steroid therapies (inhaled or topical steroids) are acceptable. See Exclusion criterion 7 for details on steroids in the setting of central nervous system (CNS) disease
Subjects with known CNS metastases are only permitted under the following conditions: Brain metastases must have been stable for the at least 2 months since completion of most recent CNS-directed intervention. Subject may be on corticosteroids so long as the dose is stable 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 the last anti-epileptic medication adjustment. Subjects with active brain metastases and/or leptomeningeal disease are excluded
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
Subject has known hypersensitivities to components of FHD-609
Subject has prior exposure to a BRD9 degrader
Subject is participating in any other clinical trials. Exceptions include participation in any observational or nontherapeutic clinical trials
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