Safety and tolerability of first‐line durvalumab with tremelimumab and chemotherapy in esophageal squamous cell carcinoma

BACKGROUND: Advanced or metastatic esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis; new first‐line systemic treatment options are needed. Combining immuno‐oncology therapies with standard chemotherapy may represent a promising approach for the treatment of solid tumors. Results from a Phase Ib study evaluating durvalumab with tremelimumab and chemotherapy in patients with advanced or metastatic ESCC are reported. METHODS: Adults with advanced or metastatic ESCC who were candidates for first‐line platinum‐based chemotherapy received durvalumab 1500 mg (Day 1), tremelimumab 75 mg (Day 1), cisplatin 80 mg/m(2) (Day 1) and 5‐fluorouracil (5‐FU) 800 mg/m(2) (Days 1–5) in 28‐day cycles until disease progression or discontinuation due to toxicity. The study consisted of safety run‐in (Part A) and expansion (Part B) periods. The primary endpoint was safety. Antitumor activity was an exploratory endpoint. RESULTS: Sixteen patients were enrolled, 6 in Part A and 10 in Part B, and received a median of 4.0 treatment cycles. All patients were Asian; median age was 65.0 years. All patients experienced adverse events (AEs) related to cisplatin and 5‐FU, and 8 (50.0%) patients experienced AEs related to durvalumab and tremelimumab. Grade ≥3 treatment‐related AEs occurred in 7 (43.8%) patients. There were no deaths associated with AEs. Six (37.5%) patients achieved an objective response. Median progression‐free survival was 3.75 months, and median overall survival was 9.69 months. CONCLUSIONS: Durvalumab with tremelimumab and chemotherapy demonstrated manageable safety and antitumor activity in patients with advanced or metastatic ESCC, warranting further investigation in randomized trials. Registered with ClinicalTrials.gov: NCT02658214.