Foghorn Therapeutics Unveils Clinical Findings From Phase 1 Trial of FHD-286 in Metastatic Uveal Melanoma
Thursday, June 29, 2023
Foghorn® Therapeutics Inc. (Nasdaq: FHTX) has released data from a Phase 1 dose escalation safety study of their drug candidate, FHD-286, in metastatic uveal melanoma (mUM). The study aimed to evaluate the safety and tolerability of FHD-286. However, the company has decided not to pursue further development of FHD-286 for uveal melanoma.
The Phase 1 study involved 73 patients with metastatic uveal melanoma who had undergone previous treatments. Different doses of FHD-286 were tested, including continuous daily doses and intermittent dosing schedules. Common treatment-related adverse events included dysgeusia, fatigue, elevated AST levels, nausea/vomiting, dry mouth, and rash. Some patients experienced grade 3 or higher treatment-related events, such as anemia, asthenia, elevated ALP levels, hypokalemia, muscular weakness, and rash.
Out of the 73 patients, 47 had target lesions for evaluation. One patient achieved a durable partial response, while nine patients experienced stable disease. Eight patients showed tumor reduction in target lesions. Reductions in circulating tumor DNA (ctDNA) were also observed, indicating a positive clinical response. Preliminary data on immune modulation markers in the tumor microenvironment suggested the potential for combining FHD-286 with checkpoint inhibitors.
The company plans to present the full results of the Phase 1 study at a future scientific meeting. Meanwhile, Foghorn intends to initiate a Phase 1 study in the third quarter of 2023 to explore the combination of FHD-286 with decitabine or cytarabine for the treatment of relapsed and/or refractory acute myeloid leukemia (AML) patients.
FHD-286 is a small-molecule inhibitor that targets BRG1 (SMARCA4) and BRM (SMARCA2), proteins involved in the regulation of gene expression within the chromatin regulatory system. Preclinical studies have shown promising anti-tumor activity of FHD-286 across a range of hematologic and solid tumors. The drug is specifically being developed for relapsed and/or refractory AML.
Uveal melanoma is a rare form of eye cancer that arises from melanin-producing cells in the eye. It is most commonly diagnosed in lightly pigmented individuals, with a median age of 55 years. Approximately 50% of uveal melanoma cases metastasize, resulting in a poor prognosis.
AML is a type of blood and bone marrow cancer that primarily affects adults. It is characterized by various genetic mutations and is diagnosed in approximately 20,000 individuals annually in the United States.
