A phase II study of zandelisib in patients with relapsed or refractory indolent non-Hodgkin lymphoma: ME-401-K02 study.

Zandelisib, a selective, potent PI3Kδ inhibitor, demonstrated favourable outcomes in patients with relapsed or refractory follicular lymphoma in a global phase II study. This phase II study evaluated the efficacy and safety of zandelisib for relapsed or refractory follicular lymphoma or marginal zone lymphoma. Sixty-one patients received zandelisib orally at 60 mg daily continuously in the first two 28-day cycles, followed by intermittent dosing on Days 1-7 following each cycle until progressive disease or unacceptable toxicity. Objective and complete response rates were 75.4% (95% confidence interval [CI], 62.7%-85.5%) and 24.6% (95% CI, 14.5%-37.3%) respectively. Median time to response was 58 days; 70.5% (43/61) of patients achieved their first response by Week 8. At least one Grade ≥ 3 treatment-emergent adverse event (TEAE) occurred in 55.7% of patients: transaminase elevation (8.2%); cutaneous reactions (3.3%); and diarrhoea, enterocolitis and lung infection (1.6% each), defined as adverse events of special interest. The discontinuation rate due to any TEAE was 14.8%. No zandelisib-related death occurred. Zandelisib showed favourable efficacy and tolerability in Japanese patients with relapsed or refractory indolent non-Hodgkin B-cell lymphoma. This unique dosing schedule may maintain efficacy while mitigating the safety issues observed with other PI3Kδ inhibitors (ClinicalTrials.gov number, NCT04533581).