Background: Standard 1L immunochemotherapy in FL is highly effective but not without significant toxicity. Up to 75% of FL patients (pts) have grade 3-5 adverse events (AEs), primarily infection and myelosuppression. More tolerable approaches are needed. PD1/PDL1 inhibitors are active in FL. A+O yield responses in 57% of rituximab-refractory FL pts (Palomba 2017). Our phase 2 study of 1L nivolumab + rituximab in FL yielded 92% overall response rate (ORR), (54% Complete Response (CR)). Toxicity compared favourably with chemotherapy: 41% grade 3-5 AEs (Hawkes 2021). FL is sensitive to low dose RT, with proven abscopal effects, is safe and synergistic with PDL1i (Hawkes 2023), potentially improving treatment efficacy with minimal extra toxicity. This investigator-led, multicentre PET-adapted phase 2 trial assessed A+O +/- RT efficacy for treatment-naïve FL. Methods:‘FLUORO’ (NCT03245021) is an open-label, multi-centre, phase 2, Simon’s 2-stage study of A+O+/-RT (N = 46; 15 in initial cohort). Key eligibility were stage II-IV grade 1-3A FL requiring therapy; ECOG ≤2; adequate organ function. All pts received 6 cycles (C) of A 1200mg + O 1000mg IV 3-weekly (plus O on C1, days 8 & 15). Pts with < CR on PET post C2 had RT (4Gy) to residual PET-avid disease. Pts with CR or PR(partial response) received 12 cycles 8-weekly maintenance O. Primary endpoint (EP) was CR rate with <5/15 CR deemed futile in 1^st stage. Secondary EP included ORR, Progression-free survival (PFS), overall survival (OS) and AEs. Exploratory EP included biomarker studies and PET radiomics. Results: 16 pts were enrolled from 08/2021-10/2022, 1 pt was replaced due to Grade(G) 4 infusion reaction to O requiring cessation. Baseline characteristics included median age 53y (range 33-79), stage IV disease in 81%, B symptoms in 12.5%, 44% had FLIPI >2. Primary EP was met, with CR at end of induction in 13/15 (87%) evaluable pts (ORR 100%). 12 pts (80%) required RT. 2 pts (13%) discontinued due to progressive disease (Table). AEs were mostly G1-2; fatigue 44%, constipation 31%, nausea 25%. fever 25%, abdominal pain 18.6%. SAEs were reported in 7/16 (44%) pts, including grade 3 infections: COVID19 12%, upper respiratory tract 12%, urinary tract 6.2%. Median follow-up is 24m (range 16-28) and ongoing, 16m PFS & OS is 87% & 100%. Biomarker analysis is ongoing. Conclusions: Atezolizumab +Obinutuzumab +/- PET-adapted 4Gy RT yielded high complete response rates with low toxicity in treatment-naïve FL. CR threshold to proceed to stage 2 was met, however was not deemed commercially viable. Clinical trial information: NCT04962126.