Background: Aberrant PI3Kδ activation is implicated in B-cell non-Hodgkin lymphomas (NHL) including FL, the most common indolent subtype. INCB050465, a selective PI3Kδ inhibitor, is being evaluated in an ongoing phase 1/2 study as monotherapy for r/r B-cell NHL, including FL (ASH 2016; Abstract 4195). Obinutuzumab plus bendamustine is approved for patients (pts) with rituximab-refractory FL. This phase 1 cohort expansion study will assess the safety, efficacy, and pharmacokinetics of INCB050465 combined with obinutuzumab and bendamustine in pts with r/r FL (NCT03039114). Methods: Eligible adults will have documented CD20+ FL r/r to 1–4 prior treatments (must include rituximab), ≥1 measurable lesion ( > 1.5 cm in ≥1 dimension), ECOG PS ≤2, and adequate hematologic, hepatic and renal function. Exclusion criteria will include: transformation of FL to aggressive lymphoma or receipt of allogeneic stem cell transplant (SCT) ≤6 months (or having graft-versus-host-disease after allogeneic or autologous SCT ≤3 months) before study start; receipt of any PI3K inhibitor, obinutuzumab, or bendamustine ≤12 months, or rituximab ≤1 month prior to study. Part 1 (safety run-in) will use a 3+3 design. Pts will receive INCB050465 PO at a dose of 20 mg QD continuously for 2 cycles (1 cycle = 4 wks) followed by 20 mg QW. Up to 2 dose reductions will be allowed. Pts will receive obinutuzumab 1000 mg IV (cycle 1: days 1, 8, and 15; cycles 2–6: day 1) and bendamustine 90 mg/m² IV (cycles 1–6: days 1 and 2). In part 2 (expansion), the safety and efficacy of INCB050465 (maximum tolerated dose) plus obinutuzumab and bendamustine will be evaluated in 30 pts, including pts treated in part 1 at the dose level deemed safe and tolerated. In both parts 1 and 2, pts not progressing after 6 cycles will be maintained on INCB050465 at the dose deemed safe and tolerated, and will continue on obinutuzumab 1000 mg IV administered on Day 1 of every second cycle for an additional 24 cycles or until disease progression. Response will be assessed using Lugano criteria (FDG-PET; CT/MRI) every 12 wks until cycle 12 and every 16 wks thereafter. The trial is open for enrollment. Clinical trial information: NCT03039114