An open-label phase Ib/II study of trastuzumab deruxtecan combined with nivolumab and CAPOX for HER2-low gastroesophageal adenocarcinoma

Background

Trastuzumab deruxtecan (T-DXd) is the standard of care for previously treated patients with HER2-positive metastatic gastroesophageal adenocarcinoma (mGEA). Exploratory analyses of the DESTINY-Gastric01 trial suggested preliminary antitumor activity of T-DXd in HER2-low mGEA. Additionally, preclinical studies have reported a synergistic effect between T-DXd and anti-programmed cell death protein 1 antibodies. Therefore, T-DXd combined with nivolumab and chemotherapy may provide therapeutic benefits for patients with HER2-low mGEA.

Trial design

EPOC2203 is a single-arm, phase Ib/II study evaluating the efficacy and safety of T-DXd combined with nivolumab and reduced-dose CAPOX as first-line treatment of patients with HER2-low mGEA. Phase Ib uses the traditional 3 + 3 design to determine the recommended phase II dose (RP2D). Patients will receive T-DXd (5.4 mg/kg, day 1) combined with nivolumab (360 mg/body, day 1) and CAPOX (capecitabine: 750 mg/m² twice daily, days 1-14 and oxaliplatin: 70 mg/m², day 1), every 3 weeks. The primary endpoints are the dose-limiting toxicity rate in phase Ib and the objective response rate (ORR) in phase II. Hypothesis testing assumes a null ORR of 58% and an alternative ORR of 80%. The planned sample size is 28 patients treated with RP2D.