Phase II study of BI1482694 in patients (pts) with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)

Background: BI1482694 (HM61713) is an oral EGFR mutant-specific TKI which has shown encouraging clinical activity as well as favorable tolerability in pts with EGFR TKI pre-treated NSCLC harboring a T790M mutation. A clinical program has been initiated to evaluate BI1482694 in various NSCLC treatment settings. This global Phase II trial is designed to further investigate the efficacy and safety of BI1482694 in pts with NSCLC and acquired T790M-mediated resistance to first-line EGFR TKIs. Trial design: This is an ongoing, single-arm, open-label, Phase II trial enrolling adult pts (≥20 years) with locally advanced or metastatic NSCLC, a documented sensitizing EGFR mutation in the tumor, disease progression following EGFR TKI therapy with or without additional lines of chemotherapy, confirmed T790M-positivity in the tumor at disease progression, and ECOG PS 0/1. Pts should not have received chemotherapy, hormonal therapy, immunotherapy, or curative radiotherapy within 14 days, EGFR TKIs (including erlotinib, gefitinib, afatinib) within 3 days, or any investigational agents within 28 days prior to study start. Prior treatment with drugs targeting T790M mutants (e.g., AZD9291, CO-1686) is not allowed. Pts will receive oral BI1482694 800 mg, with dose modification if required, once daily in 21-day cycles until disease progression, unacceptable toxicity, withdrawal or death. The primary endpoint is objective tumor response according to RECIST v1.1 (independent central review). Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, time to progression, tumor shrinkage, pt-reported outcomes, safety, and pharmacokinetics of BI1482694. This trial was initiated in June 2015 and is currently recruiting pts in the Republic of Korea. Additional study locations will include Australia, Canada, Italy, Malaysia, Spain, Taiwan, and the USA, with an estimated total enrollment of 150 pts. Further details are available at ClinicalTrials.gov (NCT02485652). Clinical trial identification: NCT02485652 Disclosure: P.A. Jånne: stock ownership in Gatekeeper Pharmaceuticals; advisory board involvement for AstraZeneca, Pfizer, Roche and Ariad; corporate-sponsored research for AstraZeneca and Astellas; and post-marketing royalties on DFCI-owned patent for LabCorp. J. Son: employment by, and stock ownership or options in, Hanmi Pharmaceutical. I. Voccia: employment by Boehringer Ingelheim. M. Uttenreuther-Fischer: employment by Boehringer Ingelheim Pharma Gmb&Co KG. K. Park: employment for Samsung Medical Center and advisory board involvement for Boehringer Ingelheim (uncompensated).