Durable Responses Seen to ME-401 in Advanced Follicular Lymphoma and CLL/SLL Patients in Ongoing Trial

MEI Pharma’s experimental compound ME-401 reduced tumor burden in 78% of patients with relapsed or refractory follicular lymphoma and in 89% of those with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in an ongoing Phase 1b trial, the company announced.

Responses were durable, updated data show, with more than half of patients in each group still responding to treatment after a median follow-up of 9.2 months for follicular lymphoma and 7.4 months for CLL/SLL patients.

“ME-401 continues to exceed expectations in the Phase 1b study,” Daniel P. Gold, PhD, president and CEO of MEI Pharma, said in a press release.

ME-401 is a potent and selective inhibitor of the protein PI3K delta, which promotes growth and survival of blood cancer cells. By blocking this protein’s activity, ME-401 is designed to prevent cancer cells from replicating, which results in their death.

Agents targeting PI3K delta also tend to kill immune cells, and as such can have fairly serious immune-related side effects. ME-401 aims for an intermittent dosing regimen that might reduce its toxicity while maintaining efficacy.

The Phase 1b trial (NCT02914938) is exploring the safety and efficacy of ME-401, given alone or in combination with either rituximab or zanubrutinib, in people with CLL/SLL, follicular lymphoma, and other B-cell non-Hodgkin’s lymphomas.

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; some patients were moved to an intermittent dosing schedule in which they took ME-401 on the first week of each four-week cycle.

To date, the trial includes a total of 55 follicular lymphoma patients and 18 CLL/SLL patients, given either ME-401 alone or in combination with rituximab. Overall responses — 78% for follicular lymphoma and 89% for CLL/SLL — were significantly higher than that reported for similar approved therapies, which range from 42% to 59% in these patient groups.

For CLL/SLL patients, responses were even better with ME-401 alone (100%) compared to the combination (75%).

As expected, efficacy was not compromised. Severe (grade 3) treatment-related adverse events — like diarrhea, rash, abnormal liver function, inflammation in the mucosas, and pneumonia —were all more common in patients receiving a continuous treatment regimen compared to the intermittent regimen.

MEI Pharma has also launched the TIDAL Phase 2 trial (NCT03768505) to explore ME-401 in relapsed or refractory follicular lymphoma patients who failed at least two prior therapies, including chemotherapy and a CD20-targeting antibody. Patients will be randomly assigned to continuous daily or to intermittent dosing cycles.

The trial, now recruiting across 48 sites worldwide, is expected to enroll 165 adults and to support a request for the treatment’s accelerated approval in the U.S.

“Currently, our primary focus is the ME-401 Phase 2 TIDAL study evaluating patients with relapsed or refractory follicular lymphoma, which may support an accelerated approval of a marketing application with FDA, as well as the continuing exploration of various combination regimens with ME-401,” Gold said.