Update results of anlotinib combined with TQB2450 (PD-L1 blockade) as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, multicenter, open-label phase II clinical trial.
Authors: Meng Xiangrui , Yang Xiuli , Hong Yong-Gui , Zhang Zhiye , Xia Jin , Chen Yunfang , Wu Tao , Shan Zheng-Zheng , Fan Qingxia , Wang Feng 
Published: July 2024

e16035 Background: Recent studies have demonstrated encouraging efficacy in patients with ESCC when combining PD-1 blockades with chemotherapy in the first-line setting. However, the safety profile of conventional chemotherapy remains unsatisfactory, suggesting the chemotherapy-free regimen a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, has shown therapeutic activity as first-line combination therapy or second-line monotherapy for ESCC patients in China. TQB2450 is a novel PD-L1 blockade developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Nanjing, China). This study aims to investigate the efficacy and safety of anlotinib plus TQB2450 as first-line therapy for patients with advanced ESCC. Preliminary results were presented at the 2023 ASCO-GI Symposium (Abs 377), the 2023 ASCO (Abs 4041) and the 2023 ESMO (1531P), the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced ESCC, whose age was between 18 and 75 years, with ECOG PS of 0 or 1 score and life expectancy of > 3 months were inclusion criteria. Eligible patients were administered with anlotinib (12mg, po, d1~14, q3w) plus TQB2450 (1200mg, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 and iRECIST using CT scans every 2 cycles for the first 6 cycles, and every 3 cycles thereafter. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 46. The primary endpoint was ORR, secondary endpoints included safety, PFS, DCR, DoR and OS. Results: From Mar 2022 to Sep 2022, a total of 46 patients were enrolled. At the data cut-off date (Dec, 2023), there were 1 CR (2.2%), 31 PR (67.4%), 10 SD (21.7%), 1 PD (2.2%) and 3 NE (6.5%). Therefore, the preliminary ORR was 69.6% (95%CI: 54.2%~82.3%), DCR was 91.3% (95%CI: 79.2%~97.6%). At the data cut-off date, 16 patients discontinued treatment due to PD, the preliminary prognostic result exhibited that the median PFS of the 46 pts was 15.44 months (95%CI: NA~NA). Additionally, safety profile exhibited that the regimen was tolerable. The common grade ≥3 treatment-related adverse events in 46 patients were hypertension (8.7%), neutrophil count decreased (4.3%), hyponatremia (4.3%), lymphocyte count decreased (4.3%), white blood cell count decreased (2.2%), platelet count decreased (2.2%), hand-foot syndrome (2.2%), hemoptysis (2.2%) and toothache (2.2%). Conclusions: The preliminary results highlighted that anlotinib plus TQB2450 as a first-line therapy for advanced ESCC showed encouraging efficacy and manageable safety profile. Furthermore, these conclusions required to be confirmed in subsequent trials. Clinical trial information: NCT05038813 .