Background: Neoadjuvant long course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) results in a complete pathological response rate in 10-30% of patients (pts), but with 20-40% non-responders and 10-15% have local recurrence. Radiotherapy (RT) is immuno-stimulatory by enhancing local/distant tumour cell death, but also immunosuppressive as it stimulates PDL1 production and myeloid-derived suppressor cell activity. Hence PDL1 inhibition may be required to enhance the immuno-stimulatory effects of RT. Hypothesis: In pts with resectable LARC, the anti-PDL1 antibody Avelumab given post LCCRT may enhance the pathological/imaging response rates whilst reducing local/distant relapse rates. Methods: Phase II single arm trial. All pts had standard LCCRT (50.4Gy RT plus 5FU [225mg/m²/day/CI] or Capecitabine [825mg/m² BID on days of RT] over 5.5 weeks). Post LCCRT (prior to surgery), pts received 4 cycles Avelumab (AV) (10mg/kg, q2 weeks), then surgical resection at 10-12 weeks post LCCRT. Fresh tumour biopsy and ctDNA sampling taken pre LCCRT, pre Cycle 1 AV and at surgery. Response by FDG PET/CT and pelvic MRI at 8 weeks post LCCRT, pre surgery. Inclusion Criteria: pts with LARC (MRI stage T3b-4/N1-2/M0), planned for LCCRT followed by curative resection, tumoural lower border within 12cm from anal verge, measurable disease (RECIST1.1), ECOG 0-1, adequate organ function and no contraindications to AV therapy. Endpoints: (a) Primary; Complete pathological response rate post-LCCRT (Target ≥ 35%), documented by central pathologist, (b) Secondary; MRI and FDG PET/CT imaging responses by RECIST1.1 and PERCIST, respectively. Toxicity. (c) Exploratory; Tumoural immune cell subsets/checkpoint expression (by multiplex immunohistochemistry and in-vitro functional assays) and ctDNA analysis. Distant relapse-free survival and the sites of relapse. ANZCTR: NCT03299660.Results: 37 pts across 6 sites, with 33 patients (89%) received allocated interventions: LCCRT, AV and surgery (where possible). Age median 55 years (31-76). M:F 23:10. Baseline tumoural stage: T3b-d 75%, T4a-b 25%. No pts with dMMR/MSI-H tumour. Overall 33 pts completed LCCRT, 31 pts (83%) completed all 4 cycles of AV and 32 pts (86%) had planned surgery (22, ULAR, 2 APR, 2 AR, 6 Other). ORR Pelvic MRI presurgery (N = 33): 2 CR, 14 PR, and 31 DCR. FDG PET/CT (N = 31): 10 CMR, 18 PMR and 3 SMD. Overall 10 pts Grade 3/4 AEs, with 15 G3/4 events. Only 3 pts with treatment-related G3 and no G4 AEs. No specific immune-related G3 AEs observed. Post-operative complications were not unexpected. Conclusions: Consolidation Avelumab post LCCRT for pts with LARC, was well tolerated with promising activity. Pathological response, biological substudies (immunological and ctDNA) and survival endpoints to be reported. Clinical trial information: NCT03299660.