ME-401, a selective oral phosphoinositide 3-kinase (PI3k)δ inhibitor, is being evaluated in a phase 1b study in patients with relapsed or refractory B-cell malignancies. This analysis reports results in follicular lymphoma.
To be eligible to participate, patients had Eastern Cooperative Oncology Group performance status 0 to 2, no prior PI3kδ therapy, and disease progression after ≥1 prior therapies. These patients were initially enrolled in a dose-escalation phase (60-180 mg) followed by 60-mg expansion cohorts, with ME-401 either given as monotherapy or in combination with rituximab.
Initially, patients received ME-401 on a daily continuous schedule until disease progression or unacceptable toxicity. Subsequently, an intermittent schedule on days 1 to 7 of a 28-day cycle was evaluated after 2 cycles or ≥3 cycles of a continuous schedule. Patients who experienced dose-limiting toxicities on the continuous schedule were managed by switching to an intermittent schedule. Conversely, patients showing disease progression (without dose-limiting toxicities) on an intermittent schedule were switched to a continuous schedule.
Eligible patients with follicular lymphoma received ME-401 alone (N = 40) or with rituximab (N = 14). Patients had a median age of 63.5 years and a median of 2 prior therapies. A total of 32 patients continued on therapy, 14 (45%) in the continuous schedule (CS) group and 18 (78%) in the intermittent schedule (IS) group. Median follow-up was 6.5 months for the CS group and 5.5 months for the IS group. Of the 22 patients who discontinued treatment, 9 had progressive disease, 4 had adverse events, 3 elected to have a stem-cell transplant, and 5 withdrew for other reasons.
Regarding adverse events of special interest, grade 3 diarrhea/colitis and rash were reported in 9 of 30 (30%) patients treated on a continuous schedule and 2 of 18 (11%) patients switched to an intermittent schedule after 2 cycles. At the data cutoff, 32 patients (59%) remained on therapy.
In the evaluable patient population, researchers documented objective response rates (ORRs) in 40 of 50 (80%) patients with follow-up disease assessment. Results were very similar for the 2 treatment groups, with a 79% ORR in patients treated with ME-401 alone and 83% in patients treated with ME-401 plus rituximab. Responses appear to be durable, with median duration of response and progression-free survival not reached.
Researchers concluded that ME-401 achieves a high rate of durable responses in relapsed or refractory follicular lymphoma. An intermittent treatment schedule appears to be a viable strategy for reducing the incidence of immune-related adverse events and maintaining responses. In some patients, response to treatments can be salvaged by reverting to a continuous schedule. A randomized phase 2 study to further evaluate ME-401 is currently enrolling patients.
Abstract 7512; Zelenetz AD, et al.