BI 1482694, a third-generation tyrosine kinase inhibitor (TKI) active against mutant epidermal growth factor receptor (EGFR), including T790M, demonstrated meaningful clinical activity with a favorable safety profile in patients with EGFR TKI-resistant non-small cell lung cancer (NSCLC) harboring T790M mutation, a study presented at the European Lung Cancer Conference (ELCC) 2016 has shown.1

T790M is the most common mechanism of acquired resistance to EGFR TKIs like gefitinib, erlotinib, and afatinib. Because BI 1482694 is active against T790M mutations, researchers sought to evaluate the tolerability and efficacy of the targeted agent in patients with T790M-positive NSCLC.

For the phase 1/2 study, researchers enrolled 76 patients with advanced EGFR mutation-positive NSCLC previously treated with EGFR TKIs. Patients were eligible whether they received additional lines of systemic therapy or not. Following the phase 1, dose-escalation portion of the study, researchers recommended 800 mg/day as the maximum tolerated dose, which was then assessed in a phase 1 expansion cohort and a phase 2 portion.

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Among the 69 patients evaluable for response, 62% had achieved an objective response rate, including 32 patients whose tumor response had been confirmed at the time of data cut-off. Of those who had a confirmed objective response, 84% were achieved by cycle 2. Disease control rate was 91%

Researchers also found that objective response rate was similar regardless of whether patients’ last treatment prior to study entry was an EGFR TKI or chemotherapy.

RELATED: Study Assesses Associations Between EGFR Mutation Subtypes, Patient Characteristics

In regard to tolerability, the most common adverse events were diarrhea, rash, nausea, and pruritus. Three patients discontinued therapy due to treatment-related adverse events, with serious events occurring in 9 patients. Of note, there were no reports of QT prolongation or hyperglycemia.

The efficacy and safety of BI 1482694 is currently being further assessed in patients with T790M-positive NSCLC in the global, phase 2 ELUXA 1 trial.


  1. Park K, Lee J, Han J, et al. Efficacy and safety of BI 1482694 (HM61713), an EGFR mutant-specific inhibitor, in T790M-positive NSCLC at the recommended phase II dose. Oral presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.