Phase Ib/Ii Trial of C-Met Inhibitor Msc2156119J and Gefitinib Vs Chemotherapy As 2Nd-Line Treatment in Asian Patients with Met-Positive (Met+), Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Nsclc) with Epidermal Growth Factor Mutation (Egfrm+) and Progression on Gefitinib

Abstract

ABSTRACT Background: The main mechanisms for the development of resistance to EGFR tyrosine kinase inhibitors (eg, gefitinib) in EGFRm+ NSCLC patients (pts) are a secondary mutation in the EGFR (ie, T790M) and amplification of the c-Met proto-oncogene. The selective, small-molecule c-Met inhibitor MSC2156119J displayed promising antitumor activity in a Phase I trial in pts with advanced solid tumors (Falchook et al. J Clin Oncol 2013:31[Suppl]:2506). This Phase Ib/II, open-label, multicenter trial evaluates the antitumor activity of MSC2156119J + gefitinib in pts with Met+ advanced EGFRm+ NSCLC (NCT01982955). Trial design: Primary objectives include determination of the recommended Phase II dose (RP2D) for the combination (Phase Ib), and progression-free survival (PFS) per investigator read (Phase II). Secondary objectives are pharmacokinetics, safety, and antitumor activity of MSC2156119J (objective response, PFS per independent read, disease control, and overall survival). Adults from mainland China, South Korea, Taiwan, and other Asian countries, with advanced NSCLC with activating EGFR mutation, ECOG status 0–1, and resistance to first-line gefitinib (Phase II only) are recruited. Key eligibility criteria include confirmed Met+ status, defined either as Met gene amplification by in situ hybridization or strong to moderate protein overexpression by immunohistochemistry, life expectancy >3 mo, and no prior EGFR-targeting therapy other than gefitinib (Phase II only). For the Phase Ib part, 15–18 pts are planned to receive 300 or 500 mg MSC2156119J p.o. + 250 mg gefitinib p.o./d (3 + 3 design; 21-d cycle). Up to 200 pts are planned to be enrolled for the Phase II part into 2 predefined subgroups according to T790M mutation status, and subsequently randomized 1:1 to 250 mg gefitinib p.o./d + RP2D MSC2156119J p.o. or 75 mg/m2 cisplatin i.v. on day 1 + 500 mg/m2 pemetrexed i.v. (max. of six 21-d cycles). The enrollment began on Dec 23, 2013. Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting. All rights reserved. Disclosure: Y. Wu: Board of Director of IASLC; President of Chinese Society of Clinical Oncology; J. Yang: Advisory board: Merck; L. Xu: Employee of Merck Serono Pharmaceutical RD U. Stammberger: Executive employee of Merck KGaA, Darmstadt, Germany; A. Johne: Employee of Merck KGaA, Darmstadt, Germany. All other authors have declared no conflicts of interest.