Fowler NH, Samaniego F, Jurczak W, et al. - This multicohort, open-label, phase 2b study was conducted to assess whether umbralisib, a dual inhibitor of phosphatidylinositol-3-kinaseδ/casein kinase-1ε, affords a safe and efficacious treatment choice for patients suffering from relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Until disease progression, unacceptable toxicity, or study withdrawal, umbralisib 800 mg was given orally once daily to a total of 208 patients experiencing R/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, or SLL) that did not respond to prior treatments (≥ 1 MZL; ≥ 2 FL/SLL), including ≥ 1 anti-CD20–based therapy. An overall response rate of 47.1% was reported. In 86.4% of patients, tumor reduction was achieved. For MZL, median progression-free survival was not reached; it was 10.6 months and 20.9 months for FL and SLL, respectively. Overall, findings demonstrated meaningful clinical activity of umbralisib in heavily pretreated patients suffering from iNHL. A manageable safety profile was displayed by umbralisib, with a relatively low incidence of immune-mediated toxicities as well as adverse event–associated discontinuations.