FHD-609 in Subjects With Advanced Synovial Sarcoma

  • STATUS
    Recruiting
  • End date
    May 31, 2025
  • participants needed
    70
  • sponsor
    Foghorn Therapeutics Inc.
Updated on 27 June 2022

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 toxicities that may occur less frequently, 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 on27 June 2022

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
Note: Inclusion criterion 15 provides timing requirements for prior therapy
in the Dose Escalation Phase and in Arm 2 of the Dose Expansion Phase
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 12) 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
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 (≤
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
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)
therapy
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
hours prior to start of study drug.)
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
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)
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
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
days after final dose of study drug
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 has known hypersensitivities to components of FHD-609
Subject has prior exposure to a BRD9 degrader
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/µL 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 is participating in any other clinical trials. Exceptions include
participation in any observational or nontherapeutic clinical trials
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note