普特利单抗联合标准化疗方案用于中危或高危儿童横纹肌肉瘤患者术前治疗的安全性和疗效：一项I/II期研究

Background: Rhabdomyosarcoma is the most common soft tissue sarcoma in pediatric populations, and intermediate or high-risk cases are associated with poor prognosis and limited therapeutic options. In this study, we aimed to evaluate the safety and efficacy of preoperative pucotenlimab combined with standard chemotherapy regimens in pediatric patients with intermediate or high-risk rhabdomyosarcoma. Methods: This is a single-arm phase I/II clinical trial (NCT06456892). Pediatric patients with intermediate or high-risk rhabdomyosarcoma received preoperative chemoimmunotherapy consisting of intravenous pucotenlimab combined with standard chemotherapy for 2-4 cycles. During the dose-escalation phase of phase I, patients were administered pucotenlimab at doses of 1, 3, and 6 mg/kg, respectively. The primary endpoints of phase I were dose-limiting toxicities (DLTs), safety, and tolerability. Secondary endpoints included pathological response and survival outcomes. Additionally, transcriptome sequencing was performed on 11 pre-treatment core needle biopsy samples and 16 post-treatment surgical tissue samples. Results: Herein, we report the adverse events and response data from the phase I/II study; survival outcomes were immature at the time of data analysis. Between June 2024 and October 2025, a total of 42 patients were enrolled, and 39 patients received at least 2 cycles of preoperative chemoimmunotherapy. To date, 21 patients have undergone surgical resection, 5 patients have not yet reached the scheduled surgical time, and the remaining patients achieved radiological complete response (CR) of the tumor or were deemed inoperable following multidisciplinary evaluation. The best overall response rate was 74.4% (29/39), and the disease control rate was 97.4% (38/39). The near-complete pathologic response (ncPR) rate was 59.1%(13/22). Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 20 patients, which were mainly attributed to chemotherapy. As of the safety data cutoff date, no DLTs were observed in any of the three dose groups. Most immune-related adverse events (irAEs) were grade 1 or 2, including hyperthyroidism (5/42,11.9%), hypothyroidism (2/42, 4.8%), and skin disorders (4/42, 9.5%). Grade 3 irAEs (elevated transaminases) occurred in 2 of 42 patients( 4.8%). Transcriptome sequencing results showed that in patients with near-complete pathologic response, the tumor microenvironment after treatment contained significantly more activated CD8+ T cells, natural killer T (NKT) cells, and Type 1 T helper (Th1) cells compared with pre-treatment. In contrast, this pre- and post-treatment difference was not significant in patients with no pathologic response. Conclusion: This study demonstrates that preoperative pucotenlimab combined with chemotherapy has an acceptable safety profile and potential efficacy in pediatric patients with intermediate or high-risk rhabdomyosarcoma, providing a promising therapeutic strategy for this patient population.