AI Article Synopsis

  • The study tested the combination of zandelisib (a PI3Kδ inhibitor) and zanubrutinib (a BTK inhibitor) to see if they would work better together and prevent resistance in patients with relapsed/refractory B-cell cancers.
  • It involved 70 patients, with a recommended dosage of 60 mg zandelisib for Days 1-7 and 80 mg zanubrutinib twice daily over a 28-day cycle.
  • The results showed an 87% response rate for follicular lymphoma and 74% for mantle cell lymphoma, with manageable side effects, indicating that the combination treatment is effective without increased toxicity.

Article Abstract

The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156518PMC
http://dx.doi.org/10.1111/bjh.19419DOI Listing

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