Abstract BACKGROUND Newly diagnosed pediatric DIPG is a fetal disease with a poor prognosis and lacks of effective treatments. Multiple studies have demonstrated that the median survival time for patients is less than one year. A single-armed, prospective, multicenter study was conducted to evaluate the efficacy and safety of adding nimotuzumab to concurrent chemoradiotherapy for the treatment of newly diagnosed pediatric DIPG. METHODS Patients were 3-15 years old, histologically or imaging confirmed newly diagnosed DIPG, Lansky score ≥ 60, and at least one measurable lesion. Totally 48 patients were enrolled. Nimotuzumab (150mg/m2/w) concurrent chemoradiotherapy (Temozolomide: 75mg/m2 per day. Radiotherapy: 54Gy/30f) were administered for 6 weeks following a maintenance treatment (Nimotuzumab: 150mg/m2 biweekly. Temozolomide: 150-200mg/m2 per day for 5 days every 28 day). The primary endpoint was ORR, with secondary endpoints including 1-year OS rate, PFS and safety. RESULTS Between Apr 3, 2021 and Apr 13, 2023, a total of 48 patients were enrolled with a median age of 7 years old, in which 20 patients radiologically diagnosed DIPG, 28 patients histopathologically confirmed DIPG with 25 (89.3%) had H3K27M mutation. The median follow-up was 15.2 months. The ORR was 31.3% (95%CI, 18.66%-46.25%), mOS was 10.35 months, 1-year OS rate was 27.4% (95%CI, 14.73%-41.73%), mPFS was 6.93 months, and 1-year PFS was 9.5% (95%CI, 2.46%-22.56%). Eight patients (16.7%) experienced grade 3 or above ADRs. The most common toxicities were neutropenia (40%), leukopenia (25.0%), thrombocytopenia (25.0%). anemia (5.0%), flank pain (5.0%). CONCLUSIONS Nimotuzumab combined with concurrent chemoradiotherapy showed survival benifit for newly diagnosed pediatric DIPG patients with tolerable toxicity.