FDA Grants ME-401 Fast Track Designation for Follicular Lymphoma

The FDA has granted ME-401 Fast Track Designation for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least 2 prior systemic therapies, according to MEI Pharma, Inc., the company developing the oral PI3K delta inhibitor.¹

In October 2019, MEI shared the latest data from a phase Ib trial showing that ME-401 induced an overall response rate (ORR) of 78% in patients with relapsed/refractory follicular lymphoma and 89% in patients with relapsed refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).²

At a median follow-up of 9.2 months (range, 3.4-20.7) and 7.4 months (range, 2.6-14.7) in the follicular lymphoma and CLL/SLL arms, respectively, the median duration of response had not yet been reached in either group among patients receiving the therapy on an intermittent schedule (IS). Regarding safety, fewer than 10% of patients experienced grade 3 adverse events (AEs) of special interest among those treated with the IS regimen.

ME-401 is currently being explored in the phase II TIDAL trial in patients with relapsed/refractory follicular lymphoma. MEI intends for data from TIDAL to support the submission of an application to the FDA for use of ME-401 in this setting.

"We are pleased to report that we have received Fast Track designation for ME-401. This designation holds several important advantages to expedite the development and regulatory review of ME-401 as we work diligently to deliver it as a new potential treatment option for patients and their physicians," Daniel P. Gold, PhD, president and chief executive officer of MEI Pharma, said in a press release. "We remain very encouraged by the maturing body of ME-401 clinical data, and we are excited to continue expanding the opportunity that ME-401 holds to provide a meaningful impact in the treatment of B-cell malignances."

Data from an earlier analysis of the phase Ib trial were reported in June 2019 at the International Conference on Malignant Lymphoma (ICML).³ Overall, the study is exploring ME-401 both as a single agent and in combination with rituximab (Rituxan) in relapsed/refractory patients with B-cell malignancies. At the time of the analysis, 85 patients had been accrued. The data presented at ICML were for 71 patients, including 54 patients with relapsed/refractory follicular lymphoma and 17 patients with relapsed/refractory CLL/SLL.

Patients received ME-401 at 60 mg once daily for two 28-day cycles followed by an IS of once daily dosing for days 1 through 7 of all subsequent cycles. An initial monotherapy cohort was administered ME-401 continuously once daily (continuous schedule; CS); some of these patients eventually switched to the IS.

There were 64 efficacy-evaluable patients, 50 with follicular lymphoma and 14 with CLL/SLL. Across both groups, the ORR was 84% among patients receiving ME-401 alone and 87% among patients receiving ME-401 plus rituximab. The ORRs in the IS and CS arms were 80% and 87%, respectively.

In the follicular lymphoma cohort, the ORR was 80%, including a 79% ORR with monotherapy and an 83% ORR with the combination. The ORR per IS and CS were 75% and 83%, respectively.

In the CLL/SLL group, the ORR was 100%, with all 11 patients receiving monotherapy and all 3 patients treated with the combination achieving a response. All 5 patients receiving the IS regimen and all 9 patients receiving the CS regimen achieved a response.

Overall, median progression-free survival was not reached with a median follow up of approximately 9 months.

The investigators considered ME-401 to be well tolerated overall, with no reported grade 4/5 AEs. Diarrhea/colitis (9.7% with IS; 20% with CS) and rash (none and 10%, respectively) were the most common grade 3 AEs of special interest. Further, IS dosing was associated with an improved rate of development of delayed grade 3 AEs.

References

1. MEI Pharma Announces Fast Track Designation Granted by U.S. FDA for ME-401 For the Treatment of Adult Patients with Relapsed or Refractory Follicular Lymphoma. Published March 31, 2020. https://bit.ly/3ayo71X. Accessed March 31, 2020.
2. MEI Pharma Announces Updated Clinical Data from ME-401 Phase 1b Study in Patients with Indolent B-cell Malignancies. Published October 3, 2019. https://bit.ly/2UuJzPE. Accessed March 31, 2020.
3. MEI Pharma Presents Updated Clinical Data from the ME-401 Phase 1b study in Patients with Indolent B-cell Malignancies at the 2019 International Conference on Malignant Lymphoma (ICML). Published June 21, 2019. https://bit.ly/2wIbYJe. Accessed March 31, 2020.