Treatment With FHD-609 Begins in Phase 1 Synovial Sarcoma Study

The first patient has been dosed in a trial of FHD-609, a selective protein degrader of bromodomain-containing protein 9, for the treatment of synovial sarcoma.

The first patient has been dosed in a trial of FHD-609, a selective protein degrader of bromodomain-containing protein 9 (BRD9), for the treatment of synovial sarcoma, according to a press release by Foghorn Therapeutics.1

FHD-609 inhibits BRG1 and BRM, which are proteins similar to ATPases. ATPases are one of the key regulators of the chromatin regulatory system. Preclinical studies have found that FHD-286 has anti-tumor activity in both hematologic and solid tumors.

“Synovial sarcoma is a rare, often aggressive malignancy with limited therapeutic options. In preclinical studies, FHD-609 has been shown to selectively degrade BRD9, taking advantage of a synthetic lethal relationship with the SS18-SSX translocation. We look forward to initial clinical data in the first half of 2022,” said Sam Agresta MD, MPH, chief medical officer of Foghorn Therapeutics in a press release.

The phase 1, open-label, single-group assignment study (NCT04879017) has an estimated enrollment of 70 participants and an estimated completion date of May 31, 2025. Primary end points include the incidence of treatment-emergent adverse events (TEAEs) up to 31 months, incidence of AEs, serious AEs, and the incidence of dose-limiting toxicities. Secondary end points include objective response rate, duration of response, time to response, progression-free survival, overall survival, and plasma concentration.

The study will have 2 parts. The dose-escalation part will be used to determine the recommended phase 2 dose and maximum tolerated dose. The dose-expansion phase will be used to evaluate safety and tolerability.

In order to participate, must be 16 years of age or older, have a diagnosis of synovial sarcoma, have metastatic or local (primary or recurrent) unresectable disease, have demonstrated progression, have discontinued their most recent therapy due to either cumulative toxicity, intolerability, or lack of clinical benefit, have measurable disease per RECIST v1.1, an ECOG status of 3 or less, and a life expectancy of 3 months or more. Additionally, patients must have adequate cardiac, renal, and hepatic function, and must use effective contraception. Patients with another malignancy that may interfere with treatment, have a severe infection, have an active HBV, HCV, or HIV infection, have an uncontrolled concurrent medical disease, central nervous system metastases, or prior exposure to a BRD9 degrader are not eligible to participate. 

“FHD-609 is our first protein degrader to enter the clinic, marking an exciting milestone for this program and further validating the potential of our Gene Traffic Control platform and our capabilities of creating precision medicines based on targeted protein degradation,” said Adrian Gottschalk, president and chief executive officer of Foghorn Therapeutics in a press release. “Foghorn has a broad pipeline of protein degrader programs, and we continue to advance these precision medicines towards clinical development.”

FHD-609 is also being studied in metastatic uveal melanoma, relapsed/refractory acute myelogenous leukemia, and myelodysplastic syndrome.

The study of the agent in synovial sarcoma is currently recruiting in Massachusetts. There are plans for recruitment in Florida, New York, Tennessee, and Texas. 

REFERENCES:
1.Foghorn Therapeutics announces first patient dosed in first-in-human clinical trial of FHD-609. News release. Foghorn Therapeutics. August 23, 2021. Accessed August 23, 2021. https://bit.ly/3gmyRFl
2.FHD-609 in Subjects With Advanced Synovial Sarcoma. ClinicalTrials.gov. Accessed August 23, 2021. https://bit.ly/3jbiAVI.