Background: Both PD-L1 and VEGFR are legitimate therapeutic targets in recurrent glioblastoma (rGB). Axitinib, a potent, selective small molecule VEGFR 1-3 inhibitor with single-agent activity in rGB, may synergize with the PD-L1 blocking IgG1 mAb avelumab for the treatment of rGB. Methods: A phase II clinical trial investigating avelumab plus axitinib in patients (pts) with rGB is ongoing (NCT03291314). Pts with rGB are stratified according to their baseline use of corticosteroids (CS). Pts without baseline CS use initiated treatment with axitinib (AXI, 5 mg po BID) plus avelumab (AVELU, 10 mg/kg IV Q2w) (Cohort A). Pts with baseline CS use initiated AXI monotherapy (AXI mono); AVELU could be added after 6w if the CS dose could be tapered to ≤ 10 mg prednisolone (Cohort B). Results: From Jun 2017 to Jan 2018, 32 pts (med age 50y [range 29-70]; 62% male; 56% WHO PS 1 or 0) initiated study treatment (16 in Cohort A and 16 in -B) . All pts had failed prior radiotherapy and temozolomide. In Cohort B, 7 pts (44%) initiated treatment with AXI+AVELU after 6w of AXI mono. Treatment with AXI+AVELU was ongoing in 10 pts (across both cohorts). Safety data are available for a total of 280 AXI+AVELU treatment weeks (median 8w [range 4-30]/pt). Treatment-related AEs (TRAE) of any grade occurred in 100% of pts. All-cause grade 3 AE occurred in 10 (43%) pts; 7 [30%] pts experienced a grade 3 TRAE. There were no gr 4 or 5 AE. PD was the only reason for stopping AXI+AVELU treatment. Conclusions: The safety profile of avelumab plus axitinib appears manageable in pts with rGB. This clinical trial is currently being continued for the evaluation of efficacy.