The FDA has placed a full clinical hold on a phase 1 trial assessing FHD-286 as a potential treatment for patients with relapsed/refractory acute myelogenous leukemia and myelodysplastic syndrome due to concerns around suspected cases of fatal differentiation syndrome that may be associated with the agent.
A phase 1 clinical trial (NCT04891757) assessing the safety and preliminary clinical activity of BRG1/BRM inhibitor FHD-286 in a population of patients with relapsed/refractory acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) has been given a full clinical hold by the FDA, according to a press release from Foghorn Therapeutics.
The hold was put in place after data were submitted in response to a partial clinical hold that was implemented following concerns of suspected fatal cases of differentiation syndrome that may have been associated with treatment with FHD-286. The FDA has stated that the clinical hold will only be lifted following further questions and analyses. Despite the full hold, a phase 1 dose escalation study assessing the agent in patients with metastatic uveal melanoma will continue per protocol. Data from the uveal melanoma trial are due to read out in the first half of 2023.
The trial has an estimated enrollment of 50 patients who were set to receive oral single-agent FHD-286. The study’s primary outcome measures were incidence of treatment-emergent adverse effects (AEs), incidence of AEs and serious AEs, and incidence of dose limiting toxicities. For the AML cohort, secondary outcomes included complete remission (CR) rate, duration of CR, CR/CR with partial hematologic recovery, transfusion independence, event-free survival (EFS), and overall survival (OS). In the MDS cohort, secondary outcomes included CR rate, CR duration, partial remission (PR) rate, PR duration, hematologic improvement, EFS, and OS.
To enroll on the study, patients were required to be 18 years or older with a confirmed diagnosis of an advanced hematologic malignancy, including those with relapsed/refractory AML for whom all prior therapies have failed or relapsed/refractory MDS for whom all previous treatments have failed including at least 4 cycles of treatment with a hypomethylating agent. Patients were also required to have an ECOG performance status of 2 or less and a life expectancy of 3 months or more. Adequate hepatic, renal, cardiovascular, respiratory, and immune system function, as well as platelet level were required.
Patients who had undergone hemopoietic stem cell transplant within 60 days of the first dose of FHD-286, were symptomatic for central nervous system leukemia, or who had immediate life-threatening leukemia complications were not eligible for enrollment on the study. Other exclusion criteria included having another malignancy that could interfere with diagnosis, active hepatitis B or C virus, active severe infection necessitating anti-infective therapy, uncontrolled intercurrent illness, or another medical or psychological condition.
Foghorn Therapeutics says FDA places clinical hold on phase 1 dose escalation study Of FHD-286. News release. Foghorn Therapeutics. August 23, 2022. Accessed August 26, 2022. https://bit.ly/3ReBEAw