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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
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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).

Zanubrutinib3

  • 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.

NCT029149384

  • 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. https://investor.meipharma.com/2021-01-04-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). https://www.meipharma.com/our-programs/me-401. Accessed Jan 6, 2021.
  3. Beigene. Zanubrutinib. https://www.beigene.com/science-and-product-portfolio/pipeline/zanubrutinib. Accessed Jan 6, 2021.
  4. Clinicaltrials.gov. A study of ME-401 in subjects with CLL/SLL, FL, and B-cell non Hodgkin's lymphoma. https://www.clinicaltrials.gov/ct2/show/study/NCT02914938. Updated Jan 6, 2021. Accessed Jan 7, 2021.

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