Phase 2 Study of ME-401 in Subjects with FL and MZL

• Research type

  Research Study

• Full title

  A Multicenter, Open-Label, Single-Arm, Phase 2 Study of Zandelisib (ME-401) in Subjects with Follicular Lymphoma or Marginal Zone Lymphoma After Failure of Two or More Prior Systemic Therapies – The TIDAL Study

• IRAS ID

  258955

• Contact name

  David Cunningham

• Contact email

  David.cunningham@rmh.nhs.uk

• Sponsor organisation

  MEI Pharma, Inc.

• Eudract number

  2018-002896-17

• ISRCTN Number

  ISRCTN00000000

• Clinicaltrials.gov Identifier

  NCT03768505

• Duration of Study in the UK

  3 years, 5 months, 1 days

• Research summary

  Research Summary
  This is a research study of an investigational drug called Zandelisib (ME-401) as a possible treatment for follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has progressed after at least 2 prior systemic therapies.
  
  ME-401 is in a class of drugs called PI3K delta inhibitors, which block a part of the cancer cell developing process and may ultimately cause lymphoma cell death. In several laboratory studies of patients with lymphoma, ME-401 has stopped lymphoma growth and controlled the disease.
  
  The main purpose of this study is to learn how well ME-401 works on controlling lymphoma and learn about the safety of the intermittent schedule (IS) dosing regimen of ME-401.
  
  All participants (approximately 120 with FL and 60 with MZL) will receive one capsule of ME-401 at 60 mg taken once a day for 2 cycles of 28 days each, for a total of 56 days. Intermittent treatment begins at cycle 3, with ME-401 administered daily for the first 7 days of every 28-day cycle (7 days on treatment and 21 days off treatment). All participants enrolled on the study under the previous protocol version in the continuous dosing schedule (CS) will switch to the IS dosing regimen with Protocol Amendment 2. Subjects who progress on IS dosing may be switched to CS dosing.
  
  This study will take place at approximately 125 centres globally with about 180 people participating. Participants are likely to be in this study for about 3-4 years. This study will consist of 28-days for screening, 18 months of dosing with ME-401, and up to 3 years of follow-up after discontinuation of ME-401. Tests include blood and urine testing, physical examinations, ECG, echocardiogram (or MUGA), and CT and PET-CT scans.

  Summary of Results
  This study showed that single-agent zandelisib has an acceptable toxicity profile when given with intermittent dosing. Certain class-specific adverse events such as diarrhea, colitis, lung infection/pneumonia, were observed both with the continuous (CS) and intermittent (IS)schedules; however, intermittent dosing appears to reduce the risk of Gr ≥3 AESIs. Overall, the adverse events observed appeaed to be tolerable and did not lead to a high rate of discontinuation. COVID 19 infection and infections of all types were reported in approximately 20% of subjects. There were 11 treatment-emergent adverse events leading to death in the study, the majority were due to COVID-19, COVID-19 pneumonia or other pathogenic pneumonia, 1 due to cardiac arrest, 1 due to tumor lysis syndrome and 1 death due to respiratory failure. Because of the premature termination of the study, efficacy data analysis and follow up was not performed and therefore the risk/benefit profile of single agent zandelisib in this population cannot be ascertained

• REC name

  North East - Tyne & Wear South Research Ethics Committee

• REC reference

  19/NE/0077

• Date of REC Opinion

  8 Apr 2019

• REC opinion

  Favourable Opinion