Background: Follicular lymphoma (FL) is the commonest indolent lymphoma, comprising 20% of non-Hodgkin Lymphoma, with approximately 80% of patients (pts) requiring therapy. At present, advanced stage is incurable; most pts require >1 treatment. Overall response rates (ORR) to standard chemoimmunotherapy (bendamustine or CHOP with rituximab or obinutuzumab) approximate 85% with considerable toxicity (grade 3-5 in 69-75%) (Hiddemann 2018). With the FL population predominantly >65 years, 10-year median survival and need for further therapy, efficacious treatments with low toxicity are desirable. PD1/PDL1 axis inhibitors are active in FL. A phase I study of obinutuzumab (O) + atezolizumab (A) induced 57% ORR in pts with rituximab-refractory FL (Palomba 2017). Our phase II ‘1^st FLOR’ study, combining nivolumab + rituximab in treatment naïve FL yielded 92% ORR, (54% Complete Response, CR). Toxicity profiles compared favourably with conventional chemotherapy: 41% grade 3-5 events (Hawkes 2021). FL is sensitive to low dose radiotherapy (RT), with abscopal effects reported, and potential to improve treatment efficacy with minimal additional toxicity when combined with PD1/PDL1 inhibitors (Sharabi 2015). This investigator initiated, multicentre single-arm phase II PET-adapted trial aims to assess the response of O + A +/- RT for treatment-naïve FL, reducing treatment-related toxicity using a chemotherapy-free, multi-modality, synergistic regimen. Methods: Eligible pts are >18 years, ECOG 0-2 with untreated, biopsy proven, grade 1-3A stage II-IV FL. Exclusions are significant compressive symptoms, autoimmune disease, pneumonitis and treatment urgency. All pts receive 6 cycles (q21 days) of O 1000mg + A 1200mg (plus O given on days 8 & 15 of cycle 1). Interim PET-CT is performed post cycle 2. Pts with less than CR will undergo RT (4Gy) to residual disease after cycle 3. At end of induction, responding patients will receive maintenance O (up to 12 cycles, 1000mg Q8W). Pts with significant progression will be taken off study. Total follow-up is 2 years post treatment. Primary endpoint is CR rate following 6 x O&A +/- RT. Secondary endpoints include ORR, PFS, OS and adverse events. PET centres are ARTnet accredited with central analysis. An extensive exploratory biomarker substudy is planned. Sample size is 46 according to a Simon’s 2-stage design. If ≥5 positive responses (CR +/- PR) without prohibitive toxicity are seen in the first 15 pts, 31 further pts will be recruited.The trial has currently enrolled 7 pts from 4 Australian sites. Clinical trial information: NCT04962126.