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Supplementary Table S4 from First-in-Maintenance Therapy for Localized High-Grade Osteosarcoma: An Open-Label Phase I/II Trial of the Anti–PD-L1 Antibody ZKAB001

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posted on 2023-04-01, 00:20 authored by Yan Zhou, Qingcheng Yang, Yang Dong, Tong Ji, Bing Zhang, Cheng Yang, Shuier Zheng, Lina Tang, Chenliang Zhou, Guowei Qian, Yujing Huang, Wenxi Yu, Hongtao Li, Yonggang Wang, Aina He, Zan Shen, Qiyuan Bao, Yingqi Hua, Hongyu Bai, Jiayi Zhao, Xiaoyi Li, Xiangrong Dai, Jianjun Zhang, Haiyan Hu, Yang Yao

Pharmacokinetic parameters after multiple administration

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National Natural Science Foundation of China (NSFC)

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ARTICLE ABSTRACT

We investigated the safety and preliminary efficacy of anti–PD-L1 antibody (ZKAB001) as maintenance therapy for localized patients with high-grade osteosarcoma to reduce the risk of recurrence and metastasis. This open-label Phase I/II study was divided into dose-escalation Phase I and expansion Phase II. Phase I used a 3+3 design with ZKAB001 at three escalating doses ranging: 5, 10, 15 mg/kg every 2 weeks in 9 patients with localized high-grade osteosarcoma and Phase II tested 10 mg/kg in 12 patients for up to 24 cycles. Primary endpoints were safety and tolerability assessed using CTCAE4.0.3. Between October 2018 and 2019, 21 eligible patients were enrolled and accepted ZKAB001 treatment: 9 in the dose-escalation phase, and 12 in expansion phase. Six patients with disease progression withdrew from this study and follow-up is ongoing. The MTD was not defined in Phase I. All doses had a manageable safety profile. The recommended dose in Phase II was set at 10 mg/kg. Most frequent immune-related adverse events were thyroiditis (76.2%) and dermatitis (42.9%). Only 1 (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year event-free survival (EFS) and overall survival (OS) were not established; however, 24-month EFS was 71.4% (95% confidence interval, 47.2–86.0) and 2-year OS was 100%. Preliminary efficacy data showed EFS benefits in patients with PD-L1 positive or an MSI-H sub-population. Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized patients with osteosarcoma.

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