Neoadjuvant cadonilimab plus anlotinib followed by surgery for locally advanced esophageal squamous cell carcinoma: A single arm, phase 2 trial.

TPS506 Background: Esophageal cancer (EC) is the seventh most common cancer in China, where most of patients have locally advanced esophageal squamous cell carcinoma (LA-ESCC) at the time of diagnosis. Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) followed by surgery is standard treatment strategy for LA-ESCC in China. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of ESCC. Programmed death 1 (PD-1) inhibitors are the most commonly used ICIs in treatment of ESCC. Lately, the phase 3 ESCORT-NEO/NCCES01 trial demonstrates that neoadjuvant PD-1 inhibitor plus chemotherapy obtains superior pCR rates compared to chemotherapy alone for LA-ESCC. Except for PD-1 inhibitors, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor is another effective ICI for ESCC, especially combined with PD-1 inhibitor according to the CHECKMATE-648 study. Although neoadjuvant immunotherapy plus chemotherapy has brought earth-shaking changes to the treatment of LA-ESCC, the chemo-based treatment modality still results in a high incidence of adverse events, reduces the quality of life and compliance of patients. Cadonilimab is a dual immune antibody drug comprised of PD-1 antibody and CTLA-4 antibody. Anlotinib is an oral, small molecule anti-angiogenic targeted agent that has been approved for use in advanced or metastatic ESCC in China. Therefore, we launched this trial to assess the efficacy and safety of cadonilimab plus anlotinib, a novel "chemo-free" strategy, followed by surgery for LA-ESCC. Methods: Study design: This is a single-arm, phase 2 study (NCT06426797). The primary endpoint of this study is the pCR rate. The secondary endpoints include safety, major pathological response (MPR) rate, objective response rate (ORR), R0 resection rate, and event-free survival (EFS). Study procedures: Cadonilimab will be intravenously administered at day 1 with a dose of 10 mg/Kg every three weeks for three cycles. Anlotinib will be orally administered daily at day 1 to day 14 with a dose of 12mg every three weeks for three cycles. In the end, the subjects will receive subtotal esophagectomy 4 to 6 weeks later after the last dose of cadonilimab. Major inclusion criteria: 1. Age > 18 years. 2. Histopathologically confirmed ESCC: c-stage II–IVA (8 th ed. AJCC). 3. Enough tissue for PD-L1 IHC test. 4. Eligible for anlotinib treatment. 5. ECOG performance status ≤ 2 points. Statistics: We hypothesized that the expected pCR rate would be 50%. 24 subjects are needed at an α-level of 0.05 (one-sided) and power of 80%. So, 25 subjects in total should be enrolled. The descriptive statistical method will be applied to the presentation of baseline characteristics, toxicities and measures of effectiveness. The Kaplan–Meier method will be used to calculate survival rates. Current enrollment: The study started on August 1 st , 2024, and 3 of planned 25 patients have been enrolled. Clinical trial information: NCT06426797 .