Abstract
BACKGROUND: Agents targeting the programmed cell death-1 pathway have demonstrated encouraging activity across multiple solid tumor types. The dose expansion phase of this phase I study evaluated the safety, tolerability, and antitumor activity of durvalumab monotherapy, and durvalumab plus tremelimumab (an anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody) combination therapy, in patients from Asia with biliary tract cancer (BTC), esophageal squamous cell carcinoma (ESCC), or head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with advanced BTC, ESCC, or HNSCC with disease progression during or following ≥1 platinum-based therapy received durvalumab monotherapy (10 mg/kg every 2 weeks) or durvalumab plus tremelimumab (durvalumab 20 mg/kg every 4 weeks [Q4W] plus tremelimumab 1 mg/kg Q4W for 4 doses, followed by durvalumab 20 mg/kg Q4W). The primary objective was safety and tolerability. Secondary objectives included antitumor activity. RESULTS: Durvalumab monotherapy was assessed in 116 patients (median age 63.5 years, 75.9% male) of whom, 42, 42, and 32 had BTC, ESCC, or HNSCC, respectively. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 19.0%, 9.5%, and 25.0% of patients with BTC, ESCC, and HNSCC, respectively. Objective response rate (ORR) was 4.8%, 7.1%, and 9.4% in BTC, ESCC, and HNSCC. Durvalumab plus tremelimumab was evaluated in 124 patients (median age 62.0 years, 79.8% male) of whom 65 had BTC and 59 had ESCC. Grade ≥3 TRAEs were reported in 23.1% and 13.6% of patients with BTC and ESCC. ORR was 10.8% and 20.3% in BTC and ESCC. There were two complete responses and 10 partial responses in ESCC, and seven partial responses in BTC. CONCLUSION: In general, durvalumab monotherapy and durvalumab plus tremelimumab combination therapy displayed acceptable safety profiles consistent with published literature, and also demonstrated clinical benefit, in patients from Asia with BTC, ESCC, or HNSCC with disease progression on ≥1 prior treatment. CLINICALTRIALS: gov Identifier: NCT01938612.