A Phase 2 Study of Osimertinib in Combination with Platinum-Pemetrexed in Patients with Uncommon Epidermal Growth Factor Receptor-Mutated Advanced Non-Small Cell Lung Cancer (NEJ067/OPAL2).

BACKGROUND:In treatment-naïve advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, approximately 10% to 15% correspond to uncommon mutations. For patients with EGFR uncommon mutations, monotherapy with either a second-generation EGFR tyrosine kinase inhibitor (TKI), afatinib, or a third-generation EGFR-TKI, osimertinib, is recommended as the initial therapy. However, needs remain unmet for patients with central nervous system (CNS) metastases and those who do not respond adequately to single-agent TKI therapy for EGFR uncommon mutations. The recently published FLAURA2 trial showed that osimertinib in combination with platinum-pemetrexed significantly prolonged progression-free survival (PFS) and provided high disease control compared with osimertinib monotherapy for common mutations. Therefore, we planned this phase II study to evaluate the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations. PATIENTS AND METHODS:Forty patients will be enrolled in the study. The primary endpoint is the objective response rate, and the secondary endpoints include safety, PFS and overall survival in overall patients, patients with and without CNS lesions at baseline and according to mutation subtype. CONCLUSIONS:In this study, we will explore the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations. Our findings may provide treatment options for patients with EGFR uncommon mutations, especially those with CNS metastases or those requiring more intensive treatment.