The phase 1/2 TakeAim Lymphoma trial examining emavusertib for patients with B-cell malignancies has received a partial clinical hold pending review by the FDA.
The FDA has placed a partial clinical hold on the phase 1/2 TakeAim Lymphoma study (NCT03328078), which is a dose escalation trial evaluating emavusertib in patients with B-cell malignancies, according to a press release from Curis.
Notification of the partial clinical hold came from the FDA Division of Hematologic Malignancies 2 that regulates clinical lymphoma studies and is separate from the FDA Division of Hematologic Malignancies 1, which regulates leukemia studies. The partial hold extends to both the TakeAim Lymphoma and Leukemia studies; Curis voluntarily paused enrollment into the lymphoma study after a partial clinical hold was placed on the phase 1/2a TakeAim Leukemia study (NCT04278768) in early in April 2022.
“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. 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], or [myelodysplastic syndrome],” James Dentzer, chief executive officer of Curis, said in the press release.
During the partial clinical hold, no new patients may be enrolled, and current patients benefiting from the treatment are allowed to continue. Emavusertib is being administered at a dose of 300 mg twice a day or lower after being reconsented.
The FDA has requested to review the study’s safety, efficacy, and other findings relating to treatment with emavusertib. In particular, the regulatory organization wants to review data pertaining to rhabdomyolysis and the recommended phase 2 dose.
The trial had an estimated enrollment of 181 patients comprising 4 cohorts. This included patients with marginal zone lymphoma in cohort 1; activated B-cell, diffuse large B-cell or extra nodal subtypes in cohort 2; primary central nervous system lymphoma in cohort 3; and those who received ibrutinib (Imbruvica) monotherapy and developed secondary resistance in cohort 4.
In part A1 of the study, investigators seek to determine the maximum tolerated dose of emavusertib. In part A2, the dose escalation portion of the trial, patients will receive a combination of 560 mg daily of oral ibrutinib plus emavusertib. The starting dose of emavusertib will be 200 mg administered twice daily. The dose expansion phase will include the recommended dose with ibrutinib to patients with non-Hodgkin lymphoma disease-specific cohorts.
In part A, the primary end points include any dose-limiting toxicities, maximum tolerated dose, and the recommended phase 2 dose. The secondary end points included the pharmacokinetic data of emavusertib measured by area under the curve, the pharmacokinetic profile measured by maximum plasma concentration, and pharmacokinetic data measured by time to maximum plasma concentration. The eligibility criteria included men or women ages 18 years or older with a life expectancy of at least 3 months and an ECOG score of 1 or less.
Curis announces FDA partial clinical hold for TakeAim lymphoma study of emvusertib (CA-4948). News Release. Curis. April 11, 2022. Accessed April 18, 2022. https://bit.ly/3M9rxKU