A clinical trial to look at the safety and potential efficacy of FHD-609 in people with advanced synovial sarcoma

Phase 1

• Conditions: Advanced Synovial Sarcoma (SS); MedDRA version: 20.0Level: PTClassification code 10042863Term: Synovial sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-001488-25-IT
• Lead Sponsor: Foghorn Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-01-19
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Subject must be >= 18 or >= 16 years of age with a minimum body weight of 50 kg.
2. 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.
3. 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.
4. 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.
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 (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.
7. Subject must have an ECOG PS of <= 2.
• Arm 2 (Dose Expansion Phase): Subject must have an ECOG PS of <= 3
8. Subject must have a life expectancy of >= 3 months.
• Arm 2 (Dose Expansion Phase): Subject must have a life expectancy of >= 2 months
9. Subject must have adequate venous access for IV drug administration and blood collection.

Please refer to the protocol for full list of inclusion criteria.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

1. 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.
2. Subject has other malignancy which may interfere with the diagnosis and/or treatment of SS and/or interpretation of outcome results.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Subject has known hypersensitivities to components of FHD-609.
9. Subject has prior exposure to a BRD9 degrader.
10. Subject is participating in any other clinical trials. Exceptions include participation in any observational or nontherapeutic clinical trials.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To determine the safety and tolerability of FHD-609 when administered as an intravenous (IV) monotherapy in subjects with advanced synovial sarcoma (SS)<br>• To identify the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of FHD-609 in subjects with advanced SS;Secondary Objective: • To determine the pharmacokinetics (PK) of FHD-609 in plasma when administered as an IV monotherapy in subjects with advanced SS<br>• To characterize the preliminary clinical activity associated with FHD-609 in subjects with advanced SS by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;Primary end point(s): Incidence of treatment-emergent adverse events (TEAEs), adverse events (AEs), dose-limiting toxicities (DLTs), serious AEs (SAEs), and<br>AEs leading to discontinuation; laboratory and other safety assessments;Timepoint(s) of evaluation of this end point: Please refer to the protocol.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Plasma concentration versus time profiles of FHD-609 will be determined to characterize the pharmacokinetic parameters for FHD-609;Timepoint(s) of evaluation of this end point: Please refer to the protocol.