Abstract CT079: ELUXA 1: Ph II study of BI1482694 (HM61713) in patients (pts) with T790M-positive non-small cell lung (NSCLC) after treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)
Authors: Ou Sai-Hong , Park Keunchil , Han Ji-Youn , Kim Dong-Wan , Bazhenova Lyudmila , Pang Yong-Kek , Hin How Soon , Juan Oscar , Son Jeewoong , Voccia Isabelle , Massey Daniel , Kim Miyoung , Jänne Pasi A. 
Published: July 2016

Background: BI 1482694 (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 development program has been initiated to evaluate BI 1482694 in various NSCLC treatment settings. In a Phase I/II trial (NCT01588145), BI 1482694 at the recommended Phase II dose of 800 mg showed encouraging activity in pts with T790M+ NSCLC: objective response rate (confirmed + unconfirmed) 62% and disease control rate 91%.1 ELUXA 1 (NCT02485652) is a global Phase II trial investigating BI 1482694 in pts with T790M+ NSCLC and progressive disease after initial EGFR TKI therapy.

Trial Design: This is an ongoing, single-arm, open-label, Phase II trial enrolling adult pts (?20 yrs) with locally advanced or metastatic EGFR mutated NSCLC, disease progression following EGFR TKI therapy with or without additional lines of chemotherapy, centrally confirmed T790M-positivity in the tumor prior to study entry and ECOG PS 0/1. Pts should have adequate organ function and at least one measurable target lesion according to RECIST v1.1. Spinal cord compression, leptomeningeal carcinomatosis, active symptomatic brain metastases, the presence or history of interstitial lung disease and prior treatment with drugs targeting T790M mutants (e.g., AZD9291, CO-1686) are not allowed. Pts will receive oral BI 1482694 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 response according to RECIST v1.1 (independent central review). Secondary endpoints include disease control, duration of response, progression-free survival, overall survival, time to progression, tumor shrinkage, pt-reported outcomes, safety and pharmacokinetics of BI 1482694. This trial was initiated in July 2015 and is currently recruiting pts in Republic of Korea, Malaysia, Philippines, Italy, Spain, Taiwan and the USA. Additional study locations will include Australia, Canada, and Germany. A Simon's two-stage design will be used to test the null hypothesis of an ORR ?30% vs the alternative that ORR is ?45%. If there are ?16 responders in the first 49 pts the trial may be stopped for futility. If the study continues beyond the first stage the primary efficacy analysis will be performed on the first 81 pts; the null hypothesis will be rejected if ?33 responders are observed. Recruitment will continue to 150 pts to provide further safety data for evaluation.

1Lee J-S, et al. Ann Oncol (2015) 26 (suppl 9): ix128-ix129

Citation Format: Sai-Hong Ou, Keunchil Park, Ji-Youn Han, Dong-Wan Kim, Lyudmila Bazhenova, Yong-Kek Pang, How Soon Hin, Oscar Juan, Jeewoong Son, Isabelle Voccia, Daniel Massey, Miyoung Kim, Pasi A. Jänne. ELUXA 1: Ph II study of BI1482694 (HM61713) in patients (pts) with T790M-positive non-small cell lung (NSCLC) after treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT079.