TakeAim Lymphoma Study Evaluating Emavusertib Pauses Enrollment of Patients With B-cell Malignancies

A voluntary partial clinical hold has been placed on the TakeAim Lymphoma study (NCT03328078) investigating emavusertib (CA-4948) for the treatment of patients with B-cell malignancies, according to a press release by Curis, Inc.¹

The announcement comes on the heels of the FDA placing a partial clinical hold on the TakeAim Leukemia study (NCT04278768) of emavusertib due to the death of a patient who experienced rhabdomyoylsis in addition to several other conditions. The safety, efficacy, and other data regarding treatment with emavusertib that the FDA requested include data from TakeAim Lymphoma.

"We reiterate our previous comments: 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," said James Dentzer, chief executive officer of Curis, 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 B-cell cancers, [acute myeloid leukemia (AML), or [myelodysplastic syndrome (MDS)]."

TakeAim Lymphoma is an open-label, dose-escalation and -expansion trial that included adult patients with relapsed or refractory hematologic malignancies like marginal zone lymphoma, activated B-cell lymphoma (ABCL), diffuse large B-cell lymphoma (DLBCL) or estrnodal subtypes, primary central nervous system lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Waldenstrom macroglobulinemia (WM).²

Before the study was halted, in part A, investigators were evaluating the safety and tolerability of emavusertib monotherapy, the maximum-tolerated dose of the agent, and the recommended phase 2 dose of the agent as coprimary end points.

In part B, the study aims to assess the coprimary end points of complete response rate achieved with emavusertib, and overall response rate (ORR).Secondary end points in the study include pharmacokinetics and the efficacy of emavusertib alone as well as in combination with ibrutinib (Imbruvica) measured by ORR, duration of response, disease control rate, progression-free survival, and overall survival at months 24 through 36. Part B of the study will also explore blood-brain barrier penetration in patients with CNS lymphoma.

While the partial clinical hold is in effect, no new patients can be enrolled in the study. Those already enrolled are patients aged 18 years or older with a life expectancy of at least 3 months, and an ECOG performance status of ≤ 1. The study excludes patients with CNS involvement other than CNS lymphoma.Those who received radiotherapy delivered to non-target lesions involving 25% or more of the bone marrow within 1 week of the study, anyone who had prior anti-cancer treatment such as chemotherapy, or immunomodulatory drug therapy within 14 days prior to the start of the study, who are on current or planned glucocorticoid therapy, or have used any investigational agent within 21 days of starting study treatment are excluded.

Patients with presence of acute or chronic toxicity caused by anti-cancer therapy must be resolved to a grade 1 to have been included in TakeAim Lymphoma. Those with known allergy or hypersensitivity to emavusertib may not enroll, nor can patients with certain B-cell non-Hodgkin lymphoma subtypes like Burkitt lymphoma, lymphoblastic lymphoma or leukemia, known primary mediastinal, ocula, or epidural DLBCL, or patients with WM who require treatment due to hyperviscosity.

Those who were already enrolled to the study before the partial clinical hold and deriving benefit from emavusertib can continue treatment at the dose of 300 mg twice daily or lower.

_REFERENCES:

_{1. Curis announces FDA partial clinical hold for takeaim lymphoma study of emavusertib (CA-4948). News release. Curis, Inc. April 11, 2022. Accessed April 11, 2022. https://bit.ly/3NV7zVQ}

_{2. A study of CA-4948 in patients with relapsed or refractory hematologic malignancies. Clinicaltrials.gov. Updated April 7, 2022. Accessed April 11, 2022. https://bit.ly/3E2J3O1}