Background: ME-401, a potent, selective, and structurally differentiated oral PI3kδ inhibitor was evaluated in a dose escalation/expansion Phase 1b study, and previously demonstrated a high objective response rate (ORR) in FL and chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) when given on a continuous (CS) or an intermittent schedule (IS). IS appeared to significantly reduce the incidence of immune-mediated adverse events of special interest (AESI) associated with PI3kδ inhibitors (diarrhea, rash, transaminase elevation, pneumonitis). We report maturing data from patients treated on the IS in this study. Methods: Eligible patients (pts) had FL, CLL/SLL, marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL), at least 1 prior therapy, adequate bone marrow and organs function, ECOG status ≤2, and no prior PI3K therapy. IS dosing: ME-401 at 60 mg/day for two 28-day cycles, followed by 7 days of therapy every 28-day cycle until disease progression or intolerance. Pts received ME-401 monotherapy (n = 21) or a combination with rituximab (n = 36) given at 375 mg/m² for 8 doses in Cycles 1-6. Results: Total of 57 pts treated with IS: 35 FL, 10 CLL/SLL, 4 MZL, and 8 DLBCL with 38 (67%) currently still ongoing. Median age: 66 years (range 38-94) and median prior therapies: 2 (range 1-8). As of January 2020, median follow-up = 9.7 mo (range 0.6-25.4+). Grade 3 AESI reported in 7 pts: 2 diarrhea (3.5%), 2 colitis (3.5%), 1 rash (2%), 1 ALT increased (2%), and 1 pneumonitis (2%). No Grade 3 AESI reported beyond Cycle 3. Discontinuation for AE in 3 pts (5%). There were no discernable safety differences between the monotherapy and rituximab combination groups. ORR was 83% in FL (76% in monotherapy group, 88% in combination group) and 89 % in CLL/SLL (100%, 83%), with median duration of response not reached. Median PFS was not reached in all patients with FL and CLL (combined analysis of both single agent and with rituximab). ORR was 100% (4/4) in MZL and 25 % (2/8) in DLBCL (in combination group only). Conclusions: ME-401 administered on an IS was well-tolerated, with a low-rate of Grade 3 class-related AESI and achieved a high-rate of durable objective responses in R/R indolent B-cell malignancies. These results may differentiate ME-401 and support further evaluation as a single-agent and in combination regimens. An ongoing global trial is evaluating ME-401 by IS in pts with FL after failure of ≥2 prior therapies (NCT03768505). Clinical trial information: NCT02914938.