FDA Grants Fast Track Designation for ME-401 in Relapsed/Refractory FL
April 01, 2020 09:00pm
By Nichole Tucker
The FDA has granted duvelisib with an orphan drug designation for the treatment of patients with T-cell lymphoma, according to a press release from Verastem Oncology, the company developing duvelisib.
The FDA has granted duvelisib (Copiktra) with an orphan drug designation for the treatment of patients with T-cell lymphoma, according to a press release from Verastem Oncology, the company developing duvelisib.1
The PI3K-δ,γ inhibitor demonstrated efficacy in a phase I study and is currently being investigated in the phase II PRIMO trial (NCT03372057).
“Receiving orphan drug designation for T-cell lymphoma, in addition to the previously-granted Fast Track status, for peripheral T-Cell lymphoma, marks another important regulatory milestone to bring Copiktra to patients who are faced with this aggressive type of disease with limited therapeutic options,” Brian Stuglik, CEO of Verastem Oncology, said in a press release. “We look forward to sharing the results of our phase II PRIMO study and efficiently advancing our development program in this indication.”
The ongoing multi-center, parallel cohort, open-label PRIMO trial is investigating the use of duvelisib in patients with relapsed or refractory peripheral T-cell lymphoma. Eligible patients are those who have received ≥2 cycles of a prior treatment regimen and either failed to achieve a partial response after ≥2 cycles, a complete response after ≥6 cycles, and/or progressed after an initial response. For those with CD30-positive anaplastic large cell lymphoma, they must have failed on, been ineligible for, or intolerant of brentuximab vedotin (Adcetris). Patients whose disease had transformed to a more aggressive lymphoma, had known central nervous system involvement, or had ongoing treatment with chronic immunosuppressants, systemic steroids, or treatment for infection were excluded from the trial.
The trial consists of a dose-optimization phase, with about 20 patients being randomly assigned to 1 of 2 cohorts, and an expansion phase. In the first cohort, patients will receive twice daily duvelisib starting at 25 mg with the potential to increase to 50 mg then 75 mg based on tolerance. Patients in the second cohort will receive 75 mg twice daily in 4-week cycles. About 90 to 100 patients are expected to be included in the expansion phase and treated with the dose determined in the dose-optimization phase.
The primary endpoint is objective response rate (ORR) and secondary endpoints include duration of response, progression-free survival, disease control rate, overall survival, and adverse events.
Findings from 2 phase I studies of duvelisib in patients with relapsed/refractory peripheral T-cell lymphoma were most recently presented at the 15th International Conference on Malignant Lymphoma.2One of the trials gave duvelisib as monotherapy continuously and the other administered duvelisib 25 mg or 75 mg twice daily for 1 month as a lead-in to a combination regimen with either romidepsin (Istodax) or bortezomib (Velcade).
Combined, 29 patients were treated with duvelisib between the 2 trials. Among those who received 75 mg single-agent duvelisib, the ORR was 54%, whereas the ORR was 44% among those who received lead-in duvelisib before romidepsin was added. Those who received 25-mg lead-in duvelisib before bortezomib had an ORR of 57%. Responses were usually observed early on, by the first treatment assessment.
The preliminary safety profile for duvelisib was considered reasonable in patients with peripheral T-cell lymphomas and was thought to be consistent with previous reports for the PI3K inhibitor.
Duvelisib has been approved by the FDA for the treatment of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma who have received at least 2 prior treatments, as well as for the treatment of patients with follicular lymphoma after at least 2 prior systemic treatment regimens.