Abstract 5180: A randomized, double-blind, placebo-controlled phase III study to evaluate AK104 plus platinum-containing chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer

Abstract Background: The current first-line standard of care for recurrent or metastatic cervical cancer is platinum-based doublet chemotherapy ± bevacizumab, but its efficacy is limited. Immunotherapies with programmed cell death receptor-1 (PD-1) inhibitor or combination of PD-1 and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors have been demonstrated to improve the clinical benefit for patients with recurrent or metastatic cervical cancer as second- or late-line treatment[1,2]. Their role in first-line treatment is under assessment. AK104 is a bispecific antibody (BsAb) that binds to both PD-1 and CTLA-4. This phase III trial aims to evaluate the efficacy and safety of AK104 plus standard chemotherapy with or without bevacizumab as first-line treatment for recurrent/metastatic cervical cancer. Trial Design: This phase III trial is a randomized, double-blind, placebo-controlled, multi-center study. Eligible patients are aged ≥ 18 and≤75 years, diagnosed with squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix, not amenable to curative surgery or concurrent chemoradiotherapy, ECOG PS 0-1, and life expectancy ≥3 months. Patients will be excluded if they have prior systemic therapy for persistent, recurrent or metastatic disease, or have previously used anti-angiogenic therapy or immune therapy. Approximately 440 patients will be randomized (1:1) to AK104 + cisplatin/carboplatin+ paclitaxel± bevacizumab or placebo + cisplatin/carboplatin + paclitaxel ± bevacizumab. The treatment will be given every 3 weeks for up to 6 cycles, followed by maintenance therapy of AK104/placebo± bevacizumab until disease progression, intolerable toxicity, loss of clinical benefit as judged by the Investigator, withdrawal of consent, or completion of 2 years treatment of AK104/placebo. The primary endpoints are blinded independent central review (BICR)-assessed progression-free survival (PFS) and overall survival (OS). Second endpoints include Investigator-assessed PFS, BICR and Investigator-assessed Objective response rate (ORR), Disease control rate (DCR), Duration of response (DoR) and Time to response (TTR), and safety and tolerability for the treatment regime. The trial is currently enrolling patients. Clinical trial information: NCT04982237. Research Sponsor: Akeso Biopharma Co,. Ltd. Citation Format: Xiaohua Wu, Jing Wang, Yi Huang, Yuzhi Li, Yang Sun, Ke Wang, Michelle Xia, Baiyong Li, Wei Liu. A randomized, double-blind, placebo-controlled phase III study to evaluate AK104 plus platinum-containing chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5180.