FDA Grants Fast Track Designation for ME-401 in Relapsed/Refractory FL

April 1, 2020
Nichole Tucker

Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.

The FDA has granted Fast Track Therapy designation to ME-401, an investigational selective oral inhibitor of phosphatidylinositol 3-kinase inhibitor as treatment of patients with relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies.

The FDA has granted Fast Track Designation to ME-401, an investigational selective oral inhibitor of phosphatidylinositol 3-kinase (PI3K) inhibitor, as a treatment of patients with relapsed or refractory follicular lymphoma (FL) who have received at least 2 prior systemic therapies, according to a press release from the drug developer, MEI Pharma.1

"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," said Daniel P. Gold, PhD, president, and CEO of MEI Pharma, in a press release.

Interim clinical data from the phase II TIDAL study of ME-401 with or without rituximab (Rituxan) for the treatment of patients with non-Hodgkin lymphoma following the failure of 2 or more prior therapies were presented at the 2019 International Conference on Malignant Lymphoma. The results were favorable. Out of 61 patients total, 48 patients with either relapsed/refractory FL or chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL, n = 13) were given ME-401 alone and 13 patients received ME-401 plus rituximab. Of the patients who were treated, 33 had received 2 or more prior therapies. Among the subjects with CLL/SLL,IGHVgene mutations were identified in 2 patients, not evaluated in 4 patients, and 7 patients did not have mutations. Overall, 64% of patients remained on treatment at data cutoff with a median follow‐up of 12.3 months (range, 1.6‐25.1) and 22 patients discontinued treatment. Nine patients had progressive disease (PD).2

Initially, a dose-escalation of ME-401 (60‐180 mg) was administered daily on a continuous schedule (CS) until PD or unacceptable toxicity. On days 1-7 of a 28-day cycle during cycle 3 or beyond, patients on CS were able to be switched to an intermittent schedule (IS). Also, to manage toxicity in the CS patients, a switch to IS was allowed. In some cases, rituximab at 375 mg/m² for 8 doses in 6 months was added to ME-401.

Objective responses were observed in 77% of the evaluable patients with FL (n = 33), and in 100% of the evaluable patients with CLL/SLL (n = 11). Among patients with FL who received ME-401 alone, the response rate was 77% and was 78% with the addition of rituximab. Of patients with PD at 24 months, the response rate was 91%. Patients who had received ≥2 prior therapies achieved a response rate of 75%.

A total of 38 patients switched from CS to IS during the study and of those patients, 87% remained on therapy for a median of 14.5 months. Due to PD, 26 patients switched back to CS from IS, 3 patients discontinued treatment as a result of continued PD following a switch to CS, and 2 patients withdrew from the study.

Grade 3 immune-related AEs (irAEs) were reported in 31.7% of patients (n = 13) on CS and 10% of the patients who were switched to IS in cycle 3 (n = 2). Most of the irAEs observed with diarrhea and colitis. Six of the patients who experienced an irAE had a break from treatment and received corticosteroid therapy. Afterward, the patients resumed treatment with ME‐401 on IS without recurrence of the irAE.

TIDAL is an ongoing global, multicenter open-label, single-arm study. The primary end points in objective response rate and the secondary end points include the duration of response, complete response rate, progression-free survival, overall survival, the overall incidence of treatment-emergent adverse events, and the pharmacokinetics of ME-401.

To be eligible for the TIDAL study, patients aged 18 years or older require histologic confirmation of FL, a minimum of 1 bi-dimensionally measurable nodal lesion, adequate hematologic, renal and hepatic function at screening, Fridericia's formula QT-interval, and a left ventricular ejection fraction ≥45%. The study excludes patients with FL grade 3b transformation, lymphomatous involvement of the central nervous system, uncontrolled illness, current or historic drug-induced pneumonitis, a history of clinically significant cardiovascular abnormalities and gastrointestinal conditions, and those with active human immunodeficiency virus.

"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 malignancies," Gold added.

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 [news release]. San Diego, California: Mei Pharma, Inc; March 31, 2020. https://bit.ly/2JuTnmr. Accessed April 1, 2020.
  2. Zelenetz AD, Jagadeesh D, Kenkre VP, et al. THE pi3kδ inhibitor ME‐401 ± rituximab in relapsed/refractory (r/r) follicular lymphoma (fl), chronic lymphocytic leukemia (cll), and small lymphocytic lymphoma (sll).Hematol Oncol, 37: 176-177. doi:10.1002/hon.133_2629