FDA Allows Trial Enrollment to Resume for Single-Agent Emavusertib in AML/MDS

FDA

The FDA has granted permission for enrollment to resume in the monotherapy phase 1a portion of the phase 1/2 TakeAim Leukemia trial (NCT04278768) evaluating the safety and efficacy of emavusertib (previously CA-4948) in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS).¹

Notably, the partial clinical hold the FDA placed on the trial in April 2022 is still in effect for the phase 1b portion of the trial investigating emavusertib in combination with azacitidine (Vidaza) or venetoclax (Venclexta).² The phase 2a dose-expansion portion of the trial also remains under partial hold until phase 1a is complete and the FDA grants approval to proceed to the next phase.

The FDA reviewed additional data provided by the Curis, Inc., related to the risk of rhabdomyolysis associated with emavusertib. The agency also examined Curis’ strategy for utilizing objective laboratory measurements to identify and manage rhabdomyolysis, if detected.

As part of the agreement between the FDA and Curis, the monotherapy portion of the trial will enroll at least 9 additional patients at 200 mg of emavusertib.

“We are pleased to announce the results of the FDA's review and to have addressed potential concerns about the identification and management of rhabdomyolysis,” James Dentzer, president and chief executive officer of Curis, stated in a press release. “We are working with our clinical sites to quickly resume enrollment of additional patients.”

When the FDA placed the partial clinical hold on the TakeAim Leukemia trial, the agency requested additional information from the study, including findings associated with the death of a patient with relapsed/refractory AML who experienced rhabdomyolysis, among other conditions. Previous results identified rhabdomyolysis as a dose-limiting toxicity associated with emavusertib.

Later in April 2022, the FDA also placed a partial clinical hold on the phase 1/2 TakeAim Lymphoma trial (NCT03328078) assessing emavusertib in patients with relapsed or refractory B-cell malignancies.³ On August, 18, 2022, the FDA lifted the partial clinical hold on TakeAim Lymphoma after Curis and the FDA agreed on a strategy for rhabdomyolysis identification and management, along with an understanding that the company will enroll at least 9 additional patients at the 200 mg dose level of emavusertib in combination with ibrutinib (Imbruvica).⁴

The open-label, dose-escalation, dose-expansion TakeAim Leukemia trial assigned patients with relapsed/refractory AML or MDS to receive emavusertib alone or in combination with azacitidine or venetoclax. If the partial clinical hold is lifted on the combination portion of the trial, investigators plan to expand to 5 cohorts: emavusertib monotherapy in patients with AML patients with spliceosome and FLT3 mutations; emavusertib monotherapy in patients with MDS and spliceosome mutations; and emavusertib combination therapy with azacitidine or venetoclax in patients without spliceosome or FLT3 mutations.

The primary objectives of the study include the safety, maximum tolerated dose, recommended phase 2 dose, and signals of activity for emavusertib.

After the partial clinical hold was lifted on the monotherapy portion of the TakeAim Leukemia study, Curis revised its timeline for the release of updated preliminary clinical data to 2023.

References

1. FDA Allows Patient Enrollment to Resume in Monotherapy Dose Escalation of Emavusertib in TakeAim Leukemia Study. News release. Curis. August 30, 2022. Accessed August 30, 2022. https://prn.to/3q19gWU
2. Curis announces FDA partial clinical hold for TakeAim Leukemia study of emavusertib (CA-4948). News release. Curis, Inc.; April 4, 2022. Accessed August 30, 2022. https://prn.to/3NG7c1g
3. Curis announces FDA partial clinical hold for TakeAim Lymphoma study of emavusertib (CA-4948). News release. Curis, Inc.; April 11, 2022. Accessed August 30 2022. https://bit.ly/3E4zrlU
4. FDA Lifts Partial Clinical Hold on the TakeAim Lymphoma Study of Emavusertib. News release. Curis, Inc. August 18, 2022. Accessed August 30, 2022. https://bit.ly/3pqraCi