FDA partially clears Curis leukemia trial in second August regulatory win
Published: Aug 30, 2022
By Chris Moore
The FDA is allowing Curis to resume dosing only for the monotherapy dose-finding phase (Phase Ia) of the trial. A partial hold will remain in place for the combination therapy phase (Phase IIb) and the expansion phase (Phase IIa) of the study until Phase 1a is complete and ready for review. This news comes two weeks after the FDA also lifted the partial clinical hold on the TakeAim Lymphoma study after reviewing the company’s latest data package.
The FDA had previously placed two separate holds on Curis: one on the TakeAim Leukemia study on April 4 and the other on the TakeAim Lymphoma study on April 11. Both studies were forced to stop enrolling new patients until the holds were lifted.
The partial hold on the lymphoma study was lifted after an agreement between Curis and the FDA on a strategy for rhabdomyolysis identification and management, as well as on the enrollment of at least nine additional patients at the 200 mg dose level of emavusertib in combination with ibrutinib.
The FDA previously cited safety concerns for the hold on the lymphoma trial. It required the company to provide more data on efficacy in regards to possible side effects such as rhabdomyolysis, which is a dose-limiting toxicity of emavusertib.
A patient in the leukemia trial died after experiencing several conditions, including rhabdomyolysis. The company said it is discussing clinical plans for emavusertib with the FDA, including the alignment of optimal dose and development path.
“We are excited to announce that FDA has completed its review of the TakeAim Lymphoma study and has lifted the partial clinical hold,” James Dentzer, president and chief executive officer of Curis, said in a statement. “We are working with our clinical sites to quickly resume enrollment of new patients in this study in the third quarter.”
The news immediately affected the company’s stock, which saw a 34 percent increase by mid-day Thursday.
The Phase I/II lymphoma study is evaluating the effects of emavusertib, an IRAK4 kinase inhibitor. It is an open-label dose-escalating trial investigating emavusertib as monotherapy and in combination with ibrutinib in patients with R/R hematologic malignancies, such as non-Hodgkin’s lymphoma and other B cell malignancies.
IRAK4 is key in the toll-like receptors and interleukin-1 receptor signaling pathways, which are frequently dysregulated in patients with cancer. The long form of IRAK4 is oncogenic and preferentially expressed in over half of patients with acute myeloid leukemia myelodysplastic syndrome.
The FDA’s Division of Hematologic Malignancies 1 (DHM1) regulates clinical studies in leukemia, and the FDA Division of Hematologic Malignancies 2 (DHM2) regulates clinical studies in lymphoma. The former placed the hold on the lymphoma study. The trial for the latter is still on hold.