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

  • Clin Cancer Res. 2023 Feb 16;29(4):764-774. doi: 10.1158/1078-0432.CCR-22-2470.
Yan Zhou  1 ,  Qingcheng Yang  2 ,  Yang Dong  2 ,  Tong Ji  3 ,  Bing Zhang  4 ,  Cheng Yang  5 ,  Shuier Zheng  1 ,  Lina Tang  1 ,  Chenliang Zhou  1 ,  Guowei Qian  1 ,  Yujing Huang  1 ,  Wenxi Yu  1 ,  Hongtao Li  1 ,  Yonggang Wang  1 ,  Aina He  1 ,  Zan Shen  1 ,  Qiyuan Bao  6 ,  Yingqi Hua  7 ,  Hongyu Bai  8 ,  Jiayi Zhao  8 ,  Xiaoyi Li  9 ,  Xiangrong Dai  9 ,  Jianjun Zhang  1  10 ,  Haiyan Hu  1  11 ,  Yang Yao  1
Affiliations
  • 1. Oncology Department of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Orthopaedic Department of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3. Department of Oral Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4. Department of Orthopaedic Oncology, the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Jiangxi, China.
  • 5. Department of Orthopaedic Oncology, Changzheng Hospital of Naval Military Medical University, Shanghai, China.
  • 6. Department of Orthopedics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 7. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Bone Tumor Institution, Shanghai, China.
  • 8. Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 9. Lee's Pharmaceutical (HK) Limited, Hong Kong Science Park, Shatin, Hong Kong.
  • 10. Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 11. Shanghai Clinical Research Ward (SCRW), Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 36469563 DOI: 10.1158/1078-0432.CCR-22-2470
Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusions: 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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