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: Yang Xiuli , Meng Xiangrui , Hong Yong-Gui , Zhang Zhiye , Xia Jin , Wu Tao , Chen Yunfang , Shan Zheng-Zheng , Fan Qingxia , Wang Feng 
Published: January 2023

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Background: PD-1 blockades combined with chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC recently. However, the safety profile of conventional chemotherapy was still disappointing. Therefore, the chemotherapy-free regimen might be a promising strategy. And it had been proved that PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) in second-line treatment for advanced ESCC showed potential efficacy and manageable toxicity. As a novel multitarget TKI mainly targeting VEGFR1-3, anlotinib was a potential first-line combination therapy and second-line monotherapy for patients with ESCC in China. TQB2450 was a novel PD-L1 blockade developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Nanjing, China), which is currently undergoing several clinical studies in China, involving ESCC and other solid tumors. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with TQB2450 as first-line therapy in advanced ESCC. 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 and life expectancy of more than 3 months were eligible as the 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 Aug 2022, a total of 36 patients were enrolled, 23 patients included in per-protocol set. In best overall response assessment, there were 14 PR (60.9%), 8 SD (34.8%) and 1 NE (4.4%). In consequence, the preliminary ORR was 60.9% (95%CI: 38.5%~80.3%), DCR was 95.7% (95%CI: 78.1%~99.9%). No patients had disease progression at the date of data cutoff. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-related adverse events in 36 patients with the incidence >10% were hypertension (33%), fatigue (17%), decreased white blood cell count (14%), hyperthyroidism (11%) and decreased neutrophil count (11%). The common grade ≥3 treatment-related adverse events were decreased platelet count (3%) and decreased lymphocyte count (3%). Conclusions: Preliminary results suggested that anlotinib combined with TQB2450 as first-line therapy in advanced ESCC exhibited encouraging efficacy and manageable adverse events. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT05038813 .