Oncology Department of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Orthopaedic Department of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clin Cancer Res. 2023 Feb 16;29(4):764-774. doi: 10.1158/1078-0432.CCR-22-2470.
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.
我们研究了抗 PD-L1 抗体（ZKAB001）作为局部高级别骨肉瘤患者维持治疗的安全性和初步疗效，以降低复发和转移的风险。
这是一项开放标签的 I/II 期研究，分为剂量递增的 I 期和扩展的 II 期。I 期采用 3+3 设计，9 例局部高级别骨肉瘤患者接受 ZKAB001 三种递增剂量治疗，范围为：5、10、15 mg/kg，每 2 周一次；II 期在 12 例患者中测试了 10 mg/kg，最长 24 个周期。主要终点是采用 CTCAE4.0.3 评估的安全性和耐受性。
2018 年 10 月至 2019 年，21 例符合条件的患者入组并接受 ZKAB001 治疗：9 例入组剂量递增期，12 例入组扩展期。6 例疾病进展的患者退出本研究，随访仍在进行中。I 期未确定最大耐受剂量。所有剂量的安全性均可控。II 期推荐剂量为 10 mg/kg。最常见的免疫相关不良事件是甲状腺炎（76.2%）和皮炎（42.9%）。21 例患者中仅有 1 例（4.8%）出现 3 级皮疹。中位 3 年无事件生存率（EFS）和总生存率（OS）尚未确定；然而，24 个月的 EFS 为 71.4%（95%置信区间，47.2-86.0），2 年 OS 为 100%。初步疗效数据显示，PD-L1 阳性或 MSI-H 亚组患者有 EFS 获益。
改用 ZKAB001 维持治疗显示出可接受的安全性，并为局部骨肉瘤患者提供了初步的临床活性证据。
