FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors

NCT04965753 | Terminated Phase 1 FDA Drug

• 1 other identifier: FHD-609-C-001
• Study Type: interventional
• Target: 55
• Locations: 4 countries
• Sites: 12

Brief 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 or advanced SMARCB1-loss tumors.

Conditions

Advanced Synovial Sarcoma

Keywords

advanced synovial sarcoma; synovial sarcoma; SS; phase 1; FHD-609; BRD9; Foghorn; Foghorn Therapeutics; SMARCB1 loss; INI1 loss; poorly differentiated chordoma; epithelioid sarcoma; malignant rhabdoid tumor; SMARCB1; INI1

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-emergent adverse events (TEAEs)

  Dose escalation and expansion

  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

  Up to 31 months

• Incidence of dose limiting toxicities (DLTs)

  During first 6 weeks of treatment for each patient in dose escalation

  6 weeks

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Up to approximately 30 months

• Duration of Response (DOR)

  Up to approximately 30 months

• Progression Free Survival (PFS)

  Up to approximately 42 months

• Time to Response (TTR)

  Up to approximately 30 months

• Overall Survival (OS)

  Up to approximately 54 months

Study Arms (1)

FHD-609

EXPERIMENTAL

Up to approximately 104 patients will be enrolled in dose escalation and expansion.

Drug: FHD-609

Interventions

FHD-609 DRUG

FHD-609 as a single, intravenously administered agent given twice-weekly (BIW). Alternative dosing regimens may be evaluated.

FHD-609

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be ≥ 18 or ≥ 16 years of age with a minimum body weight of 50 kg.
• Subject must have a diagnosis of SS or a SMARCB1-loss tumor:
• SS:
• \- Evidence of the SS18-SSX rearrangement and/or a confirmed pathologic diagnosis of SS must be available.
• May be treatment naïve or previously treated (see definition below)
• SMARCB1-loss tumor:
• A solid tumor primarily characterized by SMARCB1 loss (eg, malignant rhabdoid tumors, epithelioid sarcoma, poorly differentiated chordoma) Documentation of biallelic SMARCB1 alterations and/or corresponding protein loss, and/or a confirmed pathologic diagnosis of a solid tumor primarily characterized by SMARCB1 loss, must be available.
• Other solid tumors with SMARCB1 loss. Documentation of biallelic SMARCB1 alterations and/or corresponding protein loss must be available.
• 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 or radiation unless the lesion has progressed post treatment nor can any local treatment or radiation involving measurable lesions be anticipated. Exceptions to the requirements for measurable disease may be made in discussion with the sponsor.
• 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 \[unless contraindicated due to medical risk; other exceptions to this are at the discretion of the Sponsor\]), 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.

You may not qualify if:

• Subject (or 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/SMARCB1-loss tumors 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.
• Subjects with known CNS metastases are only permitted under the following conditions: Brain metastases must have been stable for approximately 2 months since completion of most recent CNS-directed intervention. Subject may be receiving 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 approximately 4 weeks since the last anti-epileptic medication adjustment. Subjects with active brain metastases and/or leptomeningeal disease are excluded. Exceptions to this may be made on a case-by-case basis with approval of Sponsor.
• Dose Escalation Phase: Subjects with known CNS metastases that meet the above conditions are permitted to enroll in dose escalation.
• Arm 1 and Arm 3 (Dose Expansion Phase): Subjects with known or suspected CNS metastases are excluded from Arm 1 and Arm 3.
• 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.

Sponsors & Collaborators

• Foghorn Therapeutics Inc.: lead

Study Sites (12)

City of Hope

Duarte, California, 91010, United States

Location

University of Miami Health System

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37205, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Related Publications (1)

• Livingston JA, Blay JY, Trent J, Valverde C, Agulnik M, Gounder M, Le Cesne A, McKean M, Wagner MJ, Stacchiotti S, Agresta S, Quintas-Cardama A, Reilly SA, Healy K, Hickman D, Zhao T, Ballesteros-Perez A, Khalil A, Collins MP, Piel J, Horrigan K, Lefkovith A, Innis S, Lazar AJ, Cote GM, Wagner AJ. A Phase I Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients with Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors. Clin Cancer Res. 2025 Feb 17;31(4):628-638. doi: 10.1158/1078-0432.CCR-24-2583.

  PMID: 39660994 RESULT

MeSH Terms

Conditions

Sarcoma, Synovial; Sarcoma; Rhabdoid Tumor

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Complex and Mixed

Study Officials

• Sarah Reilly, MD

  Foghorn Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label single arm dose escalation and three-arm expansion study in patients with advanced synovial sarcoma or advanced SMARCB1-loss tumors

Study Record Dates

• First Submitted: June 26, 2021
• First Posted: July 16, 2021
• Study Start: August 17, 2021
• Primary Completion: December 4, 2023
• Study Completion: December 4, 2023
• Last Updated: March 4, 2025

Record last verified: 2025-02

Locations

IT (1); US (8); FR (2); ES (1)