FDA Places Partial Clinical Hold on Study of FHD-609 in Synovial Sarcoma


A patient treated with the second highest dose level of FHD-609 had a grade 4 adverse event. Enrollment in the study of the agent in patients with synovial sarcoma or SMARCB-1 deleted tumors has been halted.

About the Phase 1 Study of FHD-609

Trial Name: A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered FHD-609 in Subjects With Advanced Synovial Sarcoma or Advanced SMARCB1-Loss Tumors

ClinicalTrials.gov Identifier: NCT04965753

Sponsor: Foghorn Therapeutics Inc.

Recruitment Contact: Foghorn Clinical Trials, +1 (888)-615-1298, clinicaltrials@foghorntx.com

Completion Date: May 31, 2025

Enrollment in a phase 1 study of FHD-609 (NCT04965753) for patients with synovial sarcoma and/or SMARCB1-deleted tumors has been paused due to a grade 4 QTc prolongation event in a patient with synovial sarcoma being treated at the second highest dose level.1

The enrollment pause and risk mitigation actions were discussed between the company, FDA, and European regulatory authorities. Consequently, a partial clinical hold was placed on the study in the United States, while allowing patients currently enrolled and benefiting from therapy to continue dosing and to remain on FHD-609.

The dose-escalation portion of the study completed enrolled and identified a maximum tolerated dose of the study agent. Patients enrolled in the affected cohort were dose-reduced. Additional safety measures were discussed with the study investigators.

At this time, the company is not planning to pursue a dose-expansion study independently.

FHD-609 inhibits 2 proteins similar to ATPases, RG1 and BRM. ATPases are one of the key regulators of the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity in both hematologic and solid tumors.2

In the multicenter, open-label, dose-escalation and dose-expansion, phase 1 trial, patients diagnosed with synovial sarcoma or a SMARCB1-loss tumor were enrolled and assessed to examine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of FHD-609.3

Enrollment was open to patients with sarcoma who had evidence of a SS18-SSX rearrangement and/or a confirmed pathologic diagnosis of sarcoma. Patients with a solid tumor primarily characterized by SMARCB1 loss, including malignant rhabdoid tumors, epithelioid sarcoma, and poorly differentiated chordoma, were required to have documentation of biallelic SMARCB1 alterations and/or corresponding protein loss. Additional enrollment criteria included measurable disease by RECIST v1.1 criteria, an ECOG performance status of 0 to 2, a life expectancy of at least 3 months, and acceptable cardiac, hepatic, renal, hematologic, and coagulation function.

Up to 104 patients were planned to be enrolled in the study and administered FHD-609 via intravenous infusion, twice weekly.

The primary end points of the study were incidence of treatment-emergent adverse events (AEs), incidence of AEs and serious AEs, including changes in safety laboratory parameters and toxicities resulting in discontinuation, and incidence of dose-limiting toxicities.

Secondary end points of the trial consisted of objective response rate, duration of response, progression-free survival, time to response, overall survival, and plasma concentration of the drug to characterize its pharmacokinetic parameters of FHD-609.

  1. Foghorn Therapeutics provides an update on FHD-609. News release. Foghorn®Therapeutics Inc. April 24, 2023. Accessed April 25, 2023. https://bit.ly/440mXs9
  2. Foghorn Therapeutics announces first patient dosed in first-in-human clinical trial of FHD-609. News release. Foghorn Therapeutics. August 23, 2021. Accessed April 25, 2023. https://bit.ly/3gmyRFl.
  3. FHD-609 in subjects with advanced synovial sarcoma or advanced SMARCB1-loss tumors. ClinicalTrials.gov. Updated March 31, 2023. Accessed April 25, 2023. https://clinicaltrials.gov/ct2/show/NCT04965753
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