85MO Cabozantinib as maintenance therapy in high grade uterine sarcoma after stabilization or response to doxorubicin +/- ifosfamide regimen: Results from EORTC 62113-55115-STBSG-GCG (NCT01979393), randomized double-blind phase II study

generation tetravalent DR5 agonist, in combination with I/T, previously demonstrated antitumor activity in classical EWS (ORR, 71.4% [5/7]) in an ongoing phase 1 study (NCT03715933).We present updated findings.Methods: Ozekibart + I/T was examined in patients (pts) with advanced/metastatic, unresectable classical (EWSR1::ETS family fusion) R/R EWS in an expansion cohort of this open-label phase 1 study.Eligible pts were aged 12 to <85 years, had received 1-2 prior lines of systemic chemotherapy (prior I/T allowed), and had no severe hepatic impairment.Pts received ozekibart 3 mg/kg on day 1 and I/T on days 1-5 of each 21-day cycle.I and/or T could be stopped after 6 cycles at investigator discretion for potential toxicity; ozekibart was continued.Safety and clinical response were primary endpoints.Results: As of data cutoff (15 Oct 2025), 32 pts had received ozekibart + I/T.Median age was 31 years (range, 13-71); median number of prior lines of therapy was 2 (prior I and/or T, n=4).Overall, 13 pts remain on treatment; 4 pts discontinued due to AEs (none related to ozekibart; 2 related to I/T) and 14 had disease progression.Consistent with the safety profile of I/T, the most common AEs were diarrhea (any grade, 78.1%; grade 3, 34.4%), nausea (68.8%; 9.4%), anemia (46.9%; 28.1%), and vomiting (43.8%; 9.4%).No grade 3 hepatotoxicity was observed.At data cutoff, 25 pts were evaluable for response.ORR with ozekibart + I/T was 68.0% (17/25; all partial responses; 1 had progressed on a prior I-containing regimen), and the disease control rate was 92.0% (23/25).One pt remained progression free after 22 months of treatment.Conclusions: Ozekibart + I/T led to high response rates in pts with R/R EWS (ORR, 68.0%), with a manageable safety profile.Our findings support further evaluation of ozekibart + I/T in R/R EWS.Updated data will be presented at ESMO Sarc.