A partial clinical hold placed on the phase 1/2 TakeAim Lymphoma trial was lifted after a strategy to identify and manage rhabdomyolysis was agreed upon.
A partial clinical hold that was previously placed by the FDA on the phase 1/2 TakeAim Lymphoma study (NCT03328078) assessing emavusertib (CA-4948) in patients with relapsed/refractory lymphoma has been lifted, according to a press release from Curis.1
The FDA had previously placed partial clinical holds on both the TakeAim Lymphoma and Leukemia studies (NCT04278768) in April 2022 following a request for additional safety and efficacy findings, with a particular concern over rhabdomyolysis, a known dose-limiting toxicity of emavusertib.2,3 The leukemia study hold was issued by the FDA Division of Hematologic Malignancies 1 whereas the hold for the lymphoma study was placed and lifted by the FDA Division of Hematologic Malignancies 2 (DHM2). After a strategy to identify and manage rhabdomyolysis was created and 9 additional patients were enrolled at the 200-mg dose level of emavusertib plus ibrutinib (Imbruvica), the partial clinical hold was lifted.
“We are excited to announce that FDA has completed its review of the TakeAim Lymphoma study and has lifted the partial clinical hold. We are working with our clinical sites to quickly resume enrollment of new patients in this study in the third quarter,” James Dentzer, president and chief executive officer at Curis, said in the press release.
With this, the study’s timeline has updated and investigators anticipate updated preliminary data readout in 2023. Part of this includes alignment on optimal dosing and development path in conjunction with DHM2.
Emavusertib is an IRAK4 kinase inhibitor, which interacts with the toll-like receptor and interleukin-1 receptor pathways that are commonly associated with cancer dysregulation.
The TakeAim Lymphoma study is assessing the use of emavusertib alone or in combination with ibrutinib in patients with relapsed/refractory non-Hodgkin Lymphoma, Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Moreover, the TakeAim Leukemia study is examining emavusertib plus or minus azacitidine (Vidaza) or venetoclax (Venclexta) in patients with relapsed/refractory acute myelogenous leukemia and myelodysplastic syndrome.
The primary outcome of the lymphoma study is to determine emavusertib’s safety and tolerability, maximum tolerated dose, recommended phase 2 dose, complete response rate, and overall response rate. Secondary outcomes are pharmacokinetic profile, duration of response, and disease control rate. Moreover, primary outcomes for the leukemia study are maximum tolerated dose, recommended phase 2 dose, maximum tolerated dose, complete response rate, duration of response, and safety. Secondary outcomes are pharmacokinetics and overall response rate.