FDA Places Partial Clinical Hold on Phase 1/2 Emavusertib Study in R/R AML, High-Risk MDS

The phase 1/2a TakeAim Leukemia trial assessing emavusertib alone or with azacitidine or venetoclax in relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndrome has been placed on a partial clinical hold by the FDA.

A partial clinical hold from the FDA has been placed on the phase 1/2a TakeAim Leukemia trial (NCT04278768) which is assessing the use of emavusertib (CA-4948) as monotherapy or in combination with azacitidine (Onureg) or venetoclax (Venclexta) for patients with relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndrome, according to a press release from Curis, Inc.

In particular, the FDA has requested additional study data related to a patient with AML who died on study with several conditions including rhabdomyolysis, a known dose-limiting toxicity associated with emavusertib. In addition, safety and efficacy data as well as other findings have been requested by the FDA to determine the agent’s recommended phase 2 dose. Although no new patients are able to enroll while the partial clinical hold is in place, those who have already entered the study who are benefitting from treatment will continue to receive emavusertib at a dose of 300 mg or lower.

“We are committed to ensuring the safety of patients in our studies and to working collaboratively with the FDA to develop therapies that meaningfully improve and extend patients’ lives,” James Dentzer, chief executive officer at Curis, said in a press release. “Given the clinical profile of emavusertib observed to date, we are hopeful that the study can be resumed soon, after appropriate review. We continue to be confident in the potential of emavusertib to address the high unmet need of patients with AML or MDS.”

Should the clinical hold be lifted and the clinical trial impact determined, Curis expects to discuss a rapid registration path for emavusertib with the FDA.

Notably, although the partial clinical hold will not impact the phase 1/2 TakeAim Lymphoma trial (NCT03328078), which is examining the use of emavusertib in those with B-cell malignancies, enrollment has been paused. The study is set to resume following resolution of the partial clinical hold.

The TakeAim Leukemia study has an estimated enrollment of 178 patients and has a 3 + 3 design. The study has several arms, including single-agent emavusertib dose-escalation and -expansion phases and dose-escalation arms for the combination of emavusertib plus either 75 mg/m2 of azacitidine intravenously or subcutaneously administered as 7 doses in a 28-day cycle or 100 mg of venetoclax on day 1 and a ramp up dose to 400 mg over 3 days for 21 days in a 28-day cycle.

The study’s primary end point is determining the maximum tolerated dose, the recommended phase 2 dose, and assessing responses and safety. Secondary outcomes include determining the pharmacokinetic profile and overall response rate.

To be eligible for the study, patients need to be 18 years or older with a life expectancy of at least 3 months and an ECOG performance status of 2 or less. Those who have been diagnosed with acute promyelocytic leukemia, active central nervous system leukemia, chronic myeloid leukemia, or who have any prior systemic anti-cancer therapies are excluded from the trial.

Reference

Curis announces FDA partial clinical hold for TakeAim Leukemia study of emavusertib (CA-4948). News release. Curis, Inc. April 4, 2022. Accessed April 5, 2022. https://prn.to/3j5i4aW