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Expansion of the phase Ib study of zandelisib (ME-401) in combination with zanubrutinib to include disease-specific B-cell malignancy cohorts

Jan 8, 2021

On January 4, 2021, it was announced that the phase Ib study arm investigating zandelisib (ME-401) in combination with zanubrutinib for the treatment of B-cell malignancies (NCT02914938) will be expanded to include disease-specific B-cell malignancy cohorts, initially follicular and mantle cell lymphoma. This was based on the recommendation by the safety review committee after completion of the safety evaluation phase.1

Zandelisib (ME-401)2

  • An oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor.
  • PI3Kδ is overexpressed in cancer cells of the B-lymphocyte lineage and is important for their proliferation and survival.
  • Granted fast tract designation by the U.S Food and Drug Administration (FDA) in March 2020 for relapsed/refractory (R/R) follicular lymphoma (FL).
  • Also being assessed as a monotherapy for the treatment of adults with R/R FL in a global phase II study (TIDAL).


  • An oral small molecule Bruton’s tyrosine kinase inhibitor.
  • Irreversibly binds to Bruton’s tyrosine kinase and blocks B-cell receptor signaling, which is crucial for the proliferation and survival of leukemic cells.
  • Being investigated in pivotal phase II and III trials in several B-cell malignancies, including Waldenstrom’s macroglobulinemia, mantle cell lymphoma, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), FL, marginal zone lymphoma, and diffuse large B-cell lymphoma.


  • Open label, non-randomized, three-armed study of:
    1. Zandelisib monotherapy in patients with R/R CLL, SLL, or FL.
    2. Zandelisib in combination with zanubrutinib in patients with R/R CLL, SLL, or B-cell non-Hodgkin lymphoma.
    3. Zandelisib in combination with rituximab in patients with R/R CLL, SLL, or B-cell non-Hodgkin lymphoma.
  • Dosage: Zandelisib once daily at 60 mg for cycles 1 and 2, and then on an intermittent schedule of once daily dosing for the first 7 days of each subsequent cycle; zanubrutinib 80 and 160 mg twice daily; rituximab 375 mg/m2 intravenously; in 28-day cycles.
  • Primary outcome measures:
    • Minimum biologically effective dose, maximum tolerated dose, and dose limiting toxicities of zandelisib alone.
    • Safety and tolerability of zandelisib combinations.
    • Maximum tolerated dose and dose limiting toxicities of zandelisib plus zanubrutinib.

Secondary outcome measure: safety profile, efficacy, and pharmacokinetics.

  1. MEI Pharma. MEI Pharma announces expansion of phase 1b study evaluating zandelisib and clinical pipeline update. Published Jan 4, 2021. Accessed Jan 6, 2021.
  2. MEI Pharma. Zandelisib (ME-401). Accessed Jan 6, 2021.
  3. Beigene. Zanubrutinib. Accessed Jan 6, 2021.
  4. A study of ME-401 in subjects with CLL/SLL, FL, and B-cell non Hodgkin's lymphoma. Updated Jan 6, 2021. Accessed Jan 7, 2021.