TENERGY: Multicenter phase II study of atezolizumab monotherapy following definitive chemoradiotherapy with 5-FU plus cisplatin in patients with locally advanced esophageal squamous cell carcinoma.

Abstract

TPS4141 Background: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are only 11% to 25%, and median overall survival (OS) is 9 to 10 months. The improved therapeutic efficacy of combining immunotherapy with radiation has been gaining interest. Our basic research suggested that sequential treatment with anti-PD-L1 agents soon after completion of CRT is the best combination. Twelve months of anti-PD-L1 antibody following platinum-based CRT significantly improved progression-free survival (PFS) and OS in patients with locally advanced non-small cell lung cancer (Antonia SJ, et al. N Engl J Med. 2018). Based on this background information, we have planned a phase II clinical trial to evaluate the safety and efficacy of atezolizumab monotherapy following definitive CRT in patients with locally advanced ESCC. Methods: The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of treatment with 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m2 on day 1 and 5-FU 700 mg/m2 on days 1–4, every 28 days), and adequate organ function. Within 4 weeks after CRT, patients will be registered in the study and started on 1200 mg of atezolizumab every three weeks until 12 months or disease progression. The primary endpoint is the CR rate by the investigator’s assessment. Overall response rate, PFS, OS, treatment-related adverse events, and CR rate by central assessment are secondary endpoints. A total of 50 patients will be enrolled, including 40 with primary locally advanced ESCC and 10 with postoperative loco regionally recurrent ESCC. As an exploratory biomarker study, biopsies from the primary site and blood collections will be performed at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab). We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutation burden, PD-L1 status, and Human Leukocyte Antigen haplotyping. Clinical trial information: UMIN000034373.