Background: Follicular lymphoma (FL) is a common type of non-Hodgkin’s lymphoma with high rates of recurrence. The conventional therapy for R/R FL is not curative. Duvelisib is a potent inhibitor of both PI3K-δ and PI3K-γ that has been approved by the FDA for pts with R/R chronic lymphocytic leukemia, R/R small lymphocytic lymphoma, and R/R FL after at least two prior therapies. The current study aimed to evaluate the efficacy and safety of duvelisib in Chinese pts with R/R FL after at least two prior therapies. The current study aimed to evaluate the efficacy and safety of duvelisib in Chinese pts with R/R FL after at least two prior therapies. Methods: This was a single-arm, open-label, multi-center, phase Ⅱ clinical trial. Adult pts (ECOG ≤ 2) with histologically confirmed FL who have progressed on or relapsed after at least two prior therapies (at least one prior therapy was rituximab-contained regimen) were recruited. The main exclusion criteria were pts with grade 3b FL or those whose condition showed a propensity to transform to aggressive lymphoma. Duvelisib 25 mg was administered orally, twice daily in a 28-day cycle (max. 12 cycles) until disease progression, intolerable toxicity, death, or withdrawal. The primary endpoint was ORR as determined by Independent Review Committee (IRC) based on the revised International Working Group response criteria for Malignant Lymphoma (IWG 2007). Secondary endpoints included ORR reported by investigators as per IWG 2007; ORR reported by IRC and investigators as per Lugano 2014 criteria; DOR; PFS; OS; TTR; and safety outcomes. Results: 23 pts (22 R/R FL and 1 diffuse large B cell lymphoma) were enrolled and included in efficacy and safety analyses (last patient first dose was on Jun 30, 2020). The median age was 49 (range, 31-70) years, and 30% were females. At the data cut-off date (Dec 30, 2020), as per IWG 2007, the ORR reported by IRC was 83%, with a best response of 6 complete responses (CR) and 13 partial responses (PR); and the ORR reported by investigators was 78%, with a best response of 18 PR. As per Lugano 2014 criteria, the ORR was 83% by IRC (7 CR + 12 PR) and 78% by investigators (2 CR + 16 PR). Median DOR, PFS, and OS have not been reached. Median TTR was 1.8 (range, 1.6-5.5) months by IRC. Treatment-related adverse events (TRAEs) of any grade occurred in 21 (91%) of 23 pts, in which 12 (52%) were ≥ grade 3. The most common ( > 20%) TRAEs were neutropenia (16, 70%), increased alanine aminotransferase (11, 48%), increased aspartate aminotransferase (10, 44%), leukopenia (7, 30%), thrombocytopenia (6, 26%), increased lactate dehydrogenase (5, 22%), and rash (5, 22%). Conclusions: Duvelisib yielded impressive anti-tumor activity with manageable safety profiles in Chinese R/R FL pts and could be a compelling treatment option in this setting. Clinical trial information: NCT04707079