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

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.