Osimertinib before and after chemoradiotherapy for unresectable stage III EGFR-mutated NSCLC: NEOLA Trial Protocol

Osimertinib, a third-generation, central nervous system-active epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, is a recommended first-line treatment for EGFR mutation-positive (EGFRm) advanced non-small cell lung cancer (NSCLC), unresectable stage III NSCLC after chemoradiotherapy (CRT), and as adjuvant treatment for resected early-stage NSCLC. NEOLA (NCT06194448) is a global, Phase II, open-label, single-arm, multicenter study, evaluating the efficacy and safety of induction osimertinib prior to CRT, and subsequent osimertinib treatment, in patients with unresectable stage III EGFRm NSCLC. Patients will be screened at 71 sites across 10 countries. Eligible patients will be aged ≥18 years with unresectable stage III EGFRm (exon 19 deletion/L858R) NSCLC eligible for definitive CRT. Patients will receive induction osimertinib (80 mg once daily) for 8 weeks, followed by 2 cycles (6 weeks) of sequential/concurrent platinum-based CRT. Patients without progressive disease (PD) can re-start osimertinib approximately 3–6 weeks after CRT until PD (per Response Evaluation Criteria in Solid Tumors 1.1) or another discontinuation criterion. The primary endpoint is 12-month progression-free survival rate. Secondary endpoints include objective response rate and disease control rate (at the end of induction), overall survival, event-free survival, and safety. The first patient was enrolled in April 2024, with primary completion expected in 2026. ClinicalTrials.gov identifier is NCT06194448 (date of registration 5 January 2024).