A single-arm, phase II trial assessing the combination of AK105 and anlotinib in first-line treatment for persistent, recurrent, or metastatic cervical cancer.

5530 Background: Anlotinib, a small molecule antiangiogenic drug, which can inhibit multiple tyrosine kinase receptor activity, had been proven effective and well-tolerant in patients with recurrent or metastatic cervical cancer who had received two or more lines of prior treatments. AK105 is a novel human immunoglobulin G1 (IgG1) anti-programmed cell death-1 (PD-1) antibody. This single-arm, phase Ⅱ clinical trial aimed to assess the efficacy and safety of AK105 plus anlotinib as fist-line therapy for persistent, recurrent, or metastatic cervical cancer. Methods: Patients with pathologically diagnosed persistent, recurrent, or metastatic cervical cancer were eligible for this study. They should have previously received platinum-based systemic chemotherapy and currently not suitable for local treatment like radiotherapy or surgery, with ECOG PS 0-1. Prior use of immune checkpoint inhibitors or antiangiogenic agents was excluded. The designed doses were: AK105, 200mg, IV, Q3W; anlotinib, 12mg, PO, QD, 2 weeks on/1 week off, Q3W. The treatment will last as long as two years, while should be halted by disease progression, or unacceptable toxicities. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression free survival (PFS), duration of response (DoR), overall survival (OS) and safety. Results: From Apr 2022 to Dec 2023, 15 patients were recruited with a median age of 50 years (range: 31-74). 9 patients were PD-L1 expression positive (CPS≥1), 1 negative and 5 NA. 73.3% patients were confirmed as squamous cell carcinoma. At the data cutoff date (Dec 29, 2023), 10 patients had received at least once tumor efficacy evaluation. 6 (6/10, 60.0%) patients achieved PR, 2 (2/10, 20.0%) patients achieved SD, and 2(2/10, 20.0%) patient PD. The ORR was 60.0% (95% IC, 26.2%-87.8%) and DCR was 80.0% (95% IC, 44.4%-97.5%). Incidence of any grades TRAEs was 86.7%. Grade 3 TRAEs incidence was 33.3% including hypertension (1/15, 6.7%), thrombocytopenia (1/15, 6.7%), elevated alanine aminotransferase (1/15, 6.7%), adrenal insufficiency (1/15, 6.7%), and rash (1/15, 6.7%), pulmonary infection (1/15, 6.7%). No Grade 4 or death occurred. Conclusions: This chemo-free therapy of AK105 plus anlotinib in the first-line treatment with persistent, recurrent, or metastatic cervical cancer showed promising efficacy with favorable toxicity profile. More data will be reported in the future. Clinical trial information: NCT05137171 .