Safety and clinical efficacy of sintilimab in pediatric patients with advanced or recurrent malignancies in a phase I study.

person Yi Que Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Yi Que, Suying Lu, Juan Wang, Feifei Sun, Jia Zhu, Junting Huang, Zijun Zhen, Yizhuo Zhang

Authors person Yi Que Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Yi Que, Suying Lu, Juan Wang, Feifei Sun, Jia Zhu, Junting Huang, Zijun Zhen, Yizhuo Zhang Organizations Sun Yat-sen University Cancer Center, Guangzhou, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Innovent Biologics, Inc. Background: This is a first phase I study investigating the safety and efficacy of sintilimab in pediatric patients with advanced or recurrent malignancies. Methods: During dose escalation, patients received a single-dose intravenous infusion of sintilimab. The planned dosing groups were 1, 3 and 10 mg/kg. During dose expansion, patients received sintilimab every three weeks. Primary endpoints were determination of dose-limiting toxicities at the maximum administered dose, safety and tolerability, and the proportion of patients with objective response to sintilimab according to the Response Evaluation Criteria in Solid Tumours version 1.1. PD-L1 expression of tumor in subjects were identified by immunohistochemistry (DACO,22C3). Whole exome sequencing (WES) was performed in 15 patients to characterize the mutational landscape and CNV status. Results: 29 patients were enrolled, including 10 patients with Hodgkin lymphoma (HL), 19 patients with other tumor types. Some special pathological types, including thymoma, choroid plexus carcinoma, and NK-T cell lymphoma are included. Patients were pretreated with a median of 3 prior lines of systemic treatment. Sintilimab was well tolerated without dose-limiting toxicity. By the safety data cutoff date, all patients experienced treatment related adverse events (TRAE) with most adverse events being grade 1 or 2, and ≥ grade 3 TRAEs occurred in 10%. Among all 27 subjects evaluated, 4 confirmed complete response (2HL, 1 NK/T lymphoma, 1 anaplastic ependymoma), 7 confirmed partial responses (4 HL, 1 Ewing sarcoma, 1 diffuse large-B lymphoma and 1 thymoma), and 7 stable disease were observed, for an objective response rate of 40.7%, and a disease control rate of 66.7%. Subjects with PD-L1-positive expression benefited more from sintilimab treatment than PD-L1-negative subjects (66.7% ORR versus 33.3% ORR, p =0.314) although statistically insignificant. The genomic profiling of WES indicatedpatients with a specific genomic mutation type predict the response of PD-1 therapy. Conclusions: Sintilimab was well tolerated and demonstrated promising anti-tumor activity in pediatric HL. The completion of the current phase I study has led to the initiation of the first prospective anti-PD-1 registration trial in Asia focusing on pediatric patients and serve as the basis for its potential study in combinatorial regimens for childhood cancer. Clinical trial information: NCT04400851. Antitumor activity Histology 1mg/kg(n= 6) 3 mg/kg(n=14 ) 10 mg/kg(n=7 ) Total(N=27) ORR,DCR Hodgkin lymphoma 1CR,1PR 1CR, 2PR,4SD 1PR 2CR, 4PR, 4SD 60%,100% Other types of tumor 1CR,1PR,2PD 1CR, 1SD, 5PD 2PR,2SD,2PD 2CR,3PR,3SD,9PD 29.4%,47.1% Total 2CR,2PR,2PD 2CR,2PR,5SD,5PD 3PR,2SD, 2PD 4CR,7PR,7SD,9PD 40.7%,66.7% ORR,DCR 66.7%,66.7% 28.6%,64.3% 42.9%,71.4% 40.7%,66.7% /

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