Olmutinib in T790M‐positive non–small cell lung cancer after failure of first‐line epidermal growth factor receptor‐tyrosine kinase inhibitor therapy: A global, phase 2 study

<jats:sec><jats:title>Background</jats:title><jats:p>In this open‐label, international phase 2 study, the authors assessed the efficacy and safety of olmutinib in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who had a confirmed T790M mutation and disease progression on previous epidermal growth factor receptor‐tyrosine kinase inhibitor therapy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients aged ≥20 years received once‐daily oral olmutinib 800 mg continuously in 21‐day cycles. The primary endpoint was the objective response rate (patients who had a confirmed best overall response of a complete or partial response), assessed by central review. Secondary endpoints included the disease control rate, the duration of objective response, progression‐free survival, and overall survival. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall, 162 patients (median age, 63 years; women, >60%) were enrolled from 68 sites in 9 countries. At the time of database cutoff, 23.5% of enrolled patients remained on treatment. The median treatment duration was 6.5 months (range, 0.03‐21.68 months). Overall, 46.3% of patients (95% CI, 38.4%‐54.3%) had a confirmed objective response (all partial responses). The best overall response (the objective response rate regardless of confirmation) was 51.9% (84 patients; 95% CI, 43.9%‐59.8%). The confirmed disease control rate for all patients was 86.4% (95% CI, 80.2%‐91.3%). The median duration of objective response was 12.7 months (95% CI, 8.3‐15.4 months). Estimated median progression‐free survival was 9.4 months (95% CI, 6.9‐12.3 months), and estimated median overall survival was 19.7 months (95% CI, 15.1 months to not reached). All patients experienced treatment‐emergent adverse events, and 71.6% of patients had grade ≥3 treatment‐emergent adverse events.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M‐positive non–small cell lung cancer who received previous epidermal growth factor receptor‐tyrosine kinase inhibitor therapy.</jats:p></jats:sec>