A Phase 2 Study of Osimertinib in Combination with Platinum + Pemetrexed in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer: The OPAL Study (NEJ032C/LOGIK1801)

Abstract Background Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is now a standard treatment for previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC). However, disease progression occurs within 19 months of treatment. In the NEJ009 study, gefitinib + carboplatin + pemetrexed demonstrated significantly better progression-free and overall survival than gefitinib monotherapy. Furthermore, LOGIK and NEJSG, major clinical trial groups in Japan conducted a randomized phase 2 study to evaluate the efficacy and safety of second-line osimertinib + carboplatin + pemetrexed vs. osimertinib monotherapy in patients with disease progression during first-line EGFR-TKI therapy and EGFR T790M resistance mutation (TAKUMI trial, jRCTs071180062). In the first treatment course for the initial 24 patients, no safety issues were reported in the combination arm. Based on this, we have planned this phase 2 study to evaluate the safety and preliminary efficacy of osimertinib + cisplatin/carboplatin + pemetrexed therapy in patients with previously untreated EGFR-mutated NSCLC Patients and methods Sixty-six patients will be enrolled, as this sample size will be adequate for assessing treatment safety and efficacy. The co-primary endpoints include safety and objective response rate, and the secondary endpoints include complete response rate, disease control rate, and progression-free survival. Conclusions This is the first study to explore the efficacy and safety of osimertinib combined with platinum-based chemotherapy in previously untreated NSCLC patients with EGFR-sensitizing mutations. Our findings could provide valuable information for phase 3 studies such as the FLAURA 2, and for developing treatment strategies for EGFR-mutated NSCLC.