Rationale and design of a phase II trial of dacomitinib in advanced non-small cell lung cancer patients with uncommon epidermal growth factor receptor mutations: a prospective and single arm study (DANCE study)

BACKGROUND: Dacomitinib is a second-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). ARCHER-1050 showed that this agent can improve progression-free survival and overall survival in advanced non-small cell lung cancer patients with sensitive EGFR mutation compared to gefitinib. However, it is unclear whether dacomitinib is effective in patients with sensitizing uncommon EGFR mutations in exon 18–21. The aim of this study is to investigate the safety and efficacy of dacomitinib in these patients. METHODS: This is a single arm, prospective, open label and phase II trial. Sample size will be calculated by a minimax two-stage design method based on the following parameters: α = 0.075, 1-β = 0.9, P0 = 0.20, P1 = 0.45 and a dropout rate of 10%. A total of 30 eligible patients will be included. Patients will receive continuous oral therapy with dacomitinib (45 mg/day) until disease progression, withdrawal of consent, or unacceptable toxicity, whichever occurs first. The primary endpoint is objective response rate (ORR) per RECIST version 1.1, as assessed by investigators’ review. The second endpoint is disease control rate (DCR), PFS, OS, and safety. DISCUSSION: We conduct a single arm, phase II study to investigate the safety and efficacy of dacomitinib in advanced NSCLC patients with sensitizing uncommon EGFR mutations. The results of the DANCE study will provide new data regarding efficacy and safety of these patients. TRIAL REGISTRATION: NCT04504071