ME-401 Experimental Compound Reduces Tumor Burden in Follicular Lymphoma, Phase 1 Trial Shows

MEI Pharma‘s experimental compound ME-401 reduced tumor burden in 80% of patients with relapsed or refractory follicular lymphoma in a Phase 1 trial, the company said. Responses were comparable among those receiving the treatment alone or in combination with Rituxan (rituximab).

Further, the data suggest that the risk of immune-related side effects can be decreased by using an intermittent treatment schedule, without any decrease in efficacy.

Findings from the Phase 1b clinical trial (NCT02914938) were presented at the recent 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, in a poster titled, “Results of the PI3Kδ inhibitor ME-401 alone or with rituximab in relapsed/refractory (R/R) follicular lymphoma (FL).”

ME-401 is an inhibitor of the protein PI3K delta, which promotes growth and survival in cancer cells. By blocking its activity, ME-401 can prevent cancer cells from replicating, and even kill them. However, drugs targeting this protein also tend to kill immune cells, so they can have fairly serious immune-related side-effects.

The study enrolled 54 follicular lymphoma patients who had experienced disease progression on at least one prior therapy. The participants were treated with ME-401, either alone (41 people) or in combination with Rituxan.

The ME-401 compound was taken orally at a dose of 60 mg. The standard treatment regimen is to take this dose continuously every day; however, some patients (27 people in total) were moved to an intermittent dosing schedule in which they only took ME-401 on the first week of each 4-week-long cycle.

Efficacy was evaluated in 50 of the participants, who were followed for a median of 9.3 months.

Oevrall, the response rate — a partial reduction of tumor burden or a complete tumor disappearance — was 80% in patients treated with only ME-401, and 78% in those concurrently treated with Rituxan.

Responses also were similar regardless of the dosing regimen, with 83% of those in a continuous dosing achieving a partial or complete response, versus 75% for those in an intermittent dosing schedule. The median time to disease progression or death was 6.5 months for ME-401 alone, and 5.5 months for the compound and Rituxan.

Overall, individuals with disease progression within 2 years of initial chemoimmunotherapy often face a poor prognosis, compared with other relapsed or refractory follicular lymphoma patients. In the trial, these patients achieved an overall response rate of 94%, meaning that 24 of the 26 participants responded to treatment.

ME-401 was generally well-tolerated, with no reported life-threatening adverse events. Serious immune-related side-effects — primarily diarrhea and intestinal inflammation, and rash – developed after the second treatment cycle in 16% of patients treated continuously. However, only 9% of people who were switched to an intermittent dosing schedule developed such side effects.

“We explored a novel dosing strategy with intermittent drug exposure (one week on, 3 weeks off) that appears to markedly reduce toxicity and maintain efficacy,” Andrew D. Zelenetz, MD, PhD, a professor at Weill Cornell Medical College and one of the investigators behind the study, said in a press release. “If validated, this could expand the role of PI3K in B-cell malignancies. A prospective randomized phase 2 trial is underway comparing intermittent to continuous dosing aiming to confirm these preliminary findings.”

MEI Pharma is now conducting a Phase 2 trial (NCT03768505) to study ME-401 as treatment for follicular lymphoma patients who failed at least two prior therapies, including chemotherapy and a CD20-targeting antibody. The TIDAL trial, now recruiting, is expected to support the treatment’s accelerated approval in the U.S.