Cadonilimab Combined with Chemotherapy with or Without Bevacizumab for First-Line Treatment of Recurrent or Metastatic Cervical Cancer

Background: The current first-line standard treatment for recurrent or metastatic cervical cancer (R/M CC) is limited.We investigated the efficacy and safety of cadonilimab,a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC. Methods: This multicenter, open-label, phase 2 study was done at 6 clinical sites in China. Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab 15mg/kg every 3 weeks (Q3W) plus chemotherapy), cohort A-10 (cadonilimb 10mg/kg Q3W plus chemotherapy), and cohort B-10 (cadonilimab 10mg/kg Q3W plus chemotherapy and bevacizumab).They received the corresponding treatments until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. The primary objective was to assess the safety, the secondary endpoints included objective overall response (ORR), duration of response (DoR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). This study is registered with ClinicalTrials.gov ( NCT04868708).Findings: From April 26, 2021 to November 5, 2021, a total 45 patients were enrolled. As of Feburary 13,2023, 44 patients underwent at least one post-baseline tumor assessment, the ORR was 66·7% in cohort A-15, 68·8% in cohort A-10, 92·3% in cohort B-10, and 79·3% in cohortA-10 and cohort B-10 combined. The treatment was effective irrespective of PD-L1 expression. The DoR was 7·62 months (95%CI 2·86-NE) in cohort A-10, and it was not reached in cohort A-15 and cohort B-10. The DCR was 100·0% in all 3 cohorts. In cohort A-15 and cohort A-10, mPFS were 11·10 and 7.06 months, the 6-month OS rates were 93·3% (95%CI 61·3-99·0) and 100·0% (95%CI 100·0-100·0), 12-month OS rates were 93·3% (95%CI 61·3-99·0) and 87·5% (95%CI 58·6-96·7), respectively. Immune-related adverse events (irAEs) occurred in 29 (64·4%) patients and treatment-related serious adverse events (TRSAEs) occurred in 23 (51·1%) patients.Interpretation: Cadonilimab combined with standard therapy was well tolerated, with encouraging antitumor activity regardless of PD-L1 expression in patients with R/M CC. A phase 3 trial of cadonilimab plus standard therapy for first-line treatment of R/M CC (NCT04982237) is ongoing.Trial Registration: This study is registered with ClinicalTrials.gov (NCT04868708).Funding: Akeso Biopharma Inc, Zhongshan, Guangdong, China.Declaration of Interest: FL,WQ, TL, WL, ZMW, BL, MX are Akeso employees.Ethical Approval: The protocol was approved by an independent ethics committee or institutional review board before initiation. The study was done in accordance with the protocol, the Declaration of Helsinki and Good Clinical Practice (GCP). All patients provided written informed consent before enrolment.