A phase II study of daily carboplatin plus irradiation followed by durvalumab for stage III non-small cell lung cancer patients with PS 2 up to 74 years old and patients with PS 0 or 1 from 75 years: NEJ039A (trial in progress)

BACKGROUND: Durvalumab is a standard drug used during maintenance therapy after chemoradiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the clinical benefits of durvalumab after chemoradiotherapy in patients with LA-NSCLC with a performance status (PS) of 2 and/or aged > 75 years. As daily carboplatin plus concurrent thoracic radiotherapy is recommended for elderly patients according to guideline, the current phase II study aims to investigate the effect of daily carboplatin plus radiotherapy followed by durvalumab for patients with stage III NSCLC who have a PS of 2 and/or are older. METHODS: Daily carboplatin plus radiotherapy followed by durvalumab is performed for the patients with stage III NSCLC who have a PS of 2 and/or are older. This is a trial in progress manuscript. STUDY TREATMENT: Daily, intravenous, low-dose carboplatin (30 mg/m(2) in a 30-min infusion) is administered to patients 1 h before radiotherapy for the first 20 fractions. Radiotherapy for all patients consisted of 60 Gy administered as 30 fractions over 6 weeks. Durvalumab at a dose of 10 mg/kg/body is intravenously administered every 2 weeks for up to 12 months after chemoradiotherapy. EXPLORATORY ASSESSMENT: In the future, an exploratory investigation will be performed to determine whether the combined assessment of T-cell markers, PD-L1 expression, and tumor mutation burden could predict the outcomes of the regimen. DISCUSSION: The results of our study will exhibit the efficacy and tolerability of durvalumab as maintenance therapy after daily carboplatin plus radiotherapy. TRIAL REGISTRATION: During the first registration (before induction chemoradiotherapy), 70 patients will be included; then, we include 58 patients during the second registration (before durvalumab treatment after chemoradiotherapy). https://jcrb.niph.go.jp/. PRIMARY ENDPOINT: The primary endpoint of the current study is the 12-month progression-free survival (PFS) rate after the initiation of durvalumab. SECONDARY ENDPOINTS: The secondary endpoints are the feasibility, objective response, PFS, overall survival, and adverse events.