Sintilimab combined with bevacizumab in relapsed or persistent ovarian clear cell carcinoma (INOVA): a multicentre, single-arm, phase 2 trial - 01/10/24

Doi : 10.1016/S1470-2045(24)00437-6

Zikun Peng, MD ^a,^{*
Contributed equally as joint first authors}, Huayi Li, MD ^a,^{*
Contributed equally as joint first authors}, Yunong Gao, MD ^b,^{*
Contributed equally as joint first authors}, Li Sun, MD ^c,^{*
Contributed equally as joint first authors}, Jie Jiang, MD ^d,^{*
Contributed equally as joint first authors}, Bairong Xia, MD ^e,^{*
Contributed equally as joint first authors}, Yi Huang, MD ^f, Yu Zhang, MD ^g, Yu Xia, PhD ^a, Yuxin Zhang, MD ^a, Yiyang Shen, BS ^a, Bowen Huang, BS ^a, Jiayu Nie, BS ^a, Xinrong Chen, BS ^a, Xingyu Liu, MD ^a, Cui Feng, MD ^h, Zhen Li, MD ^h, Wei Zhang, MD ^a, Kangjia Tao, MS ^a, Qiuxue Zhang, PhD ^a, Shican Duan, BS ^a, Yaheng Chen, MD ^a, Yeshan Chen, MD ⁱ, Wei Wang, MD ^b, Hong Zheng, MD ^b, Yudong Lu, PhD ^a, Yi Liu, MD ^c, Limei Wang, MD ^d, Wencai Qi, MD ^e, Yang He, MD ^f, Yan Tian, MD ^g,
NUWA Platform Research Group
Ting Hu, Shaoqing Zeng, Ya Wang, Jianhua Chi, Xiaofei Jiao, Jiahao Liu, Ming Li, Yuanjia Wen, Fan Xiong, Yu Xu, Guanchen Ma, Yingjun Zhao, Yang Yu, Ruyuan Li

Guiling Li, ProfMD ^i,^{^{†
Contributed equally as joint senior authors}}, Ding Ma, ProfMD ^a,^{^{†
Contributed equally as joint senior authors}}, Qinglei Gao, ProfMD ^a,^{^{†
Contributed equally as joint senior authors},}⁎

^a Department of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

^b Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gynaecological Oncology, Peking University Cancer Hospital and Institute, Beijing, China

^c Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China

^d Department of Obstetrics and Gynaecology, Qilu Hospital, Shandong University, Jinan, China

^e Department of Gynaecology Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

^f Department of Gynaecological Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

^g Department of Gynaecology, Xiangya Hospital, Central South University, Changsha, China

^h Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

ⁱ Department of Gynaecological Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

^* Correspondence to: Prof Qinglei Gao, Department of Obstetrics and Gynaecology, National Clinical Research Centre for Obstetrics and Gynaecology, Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumour Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Department of Obstetrics and Gynaecology National Clinical Research Centre for Obstetrics and Gynaecology Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education) Hubei Key Laboratory of Tumour Invasion and Metastasis Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Summary

Background

Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma.

Methods

In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18–75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0–2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing.

Findings

Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8–57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5–23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred.

Interpretation

Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy.

Funding

National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics.

Translation

For the Chinese translation of the abstract see Supplementary Materials section.

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Vol 25 - N° 10

P. 1288-1297 - octobre 2024 Retour au numéro

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Sintilimab combined with bevacizumab in relapsed or persistent ovarian clear cell carcinoma (INOVA): a multicentre, single-arm, phase 2 trial - 01/10/24

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