Safety and efficacy of pucotenlimab combined with standard chemotherapy regimens in the neoadjuvant treatment of pediatric patients with intermediate or high-risk rhabdomyosarcoma: A phase I/II study.

10038 Background: Previously, we defined the pathological complete response rate (pCR) for pediatric patients with intermediate or high-risk rhabdomyosarcoma who underwent preoperative chemotherapy alone（SIOP- 2024-ID 582). In this study, we aimed to determine the effect of preoperative pucotenlimab combined with the standard chemotherapy regimen as neoadjuvant treatment on the safety and pCR of rhabdomyosarcoma. Methods: In this single-arm phase I/II trial (NCT06456892), patients with rhabdomyosarcoma received neoadjuvant chemoimmunotherapy with pucotenlimab combined with standard chemotherapy intravenously on the first day of each three-week cycle for three cycles. During the dose-escalation phase, patients were infused with pucotenlimab at doses of 1, 3, and 6 mg/kg respectively. The primary endpoints in phase I were dose-limiting toxicities (DLTs) as well as the evaluation of safety and tolerability. Secondary endpoints included pathological complete response (pCR), major pathological response (MPR), and survival outcomes. Results: Herein, we report the adverse events and pCR in the phase I study. At the time of data analysis, the survival outcomes were not yet mature. Between June 2024 and September 2024, 15 patients were enrolled and received neoadjuvant chemoimmunotherapy. Among them, 7 patients have proceeded to surgical resection. The pCR rate was 3/7（42.9%）, and 1/7（14.3%） patients achieved an mPR. Treatment-related adverse events of grade 3 or 4 occurred in 11 patients，which mainly due to the chemotherapy. By the safety data cutoff, no DLTs were observed in the three dose groups. Most immune-related adverse events were grade 1 or 2, including hyperthyroidism (2/15), hypothyroidism (1/15), and fever (11/15). Conclusions: This study demonstrates the safety and potential efficacy of neoadjuvant pucotenlimab plus chemotherapy, with an acceptable safety profile, in patients with pediatric rhabdomyosarcoma. Clinical trial information: NCT06456892 . Summary of safety profile of 15 patients received pucotenlimab combined with the standard chemotherapy regimen. Adverse effects Grade 1 Grade 2 Grade 3 Grade 4 Decreased White Blood Cell Count 0 0 2 9 Decreased Platelet Count 3 0 1 2 Toothache 1 0 0 0 Limb Pain 2 0 0 0 Abdominal Pain 4 0 0 0 Headache 2 0 0 0 Oral Pain 0 1 0 0 Taste Disorder 1 0 0 0 Dizziness 2 0 0 0 Dysphagia 1 0 0 0 Epistaxis 1 0 0 0 Fatigue 2 0 0 0 Fever 11 2 0 0 Cough 2 0 0 0 Decreased Hemoglobin Concentration 2 8 4</j