Phase I/II multicenter, randomized, open-label trial of the c-Met inhibitor MSC2156119J and gefitinib versus chemotherapy as second-line treatment in 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.

TPS8121 Background: Resistance to EGFR tyrosine kinase inhibitors (eg, gefitinib) in EGFRm+ NSCLC patients (pts) is mainly caused by a secondary mutation in the EGFR (ie, T790M) or by activation of the c-Met/HGF signaling pathway (eg, protein overexpression and/or amplification). MSC2156119J, a highly selective small-molecule c-Met inhibitor, displayed promising antitumor activity in pts with advanced solid tumors in a Phase I trial (Falchook et al. J Clin Oncol 2013:31(Suppl):2506). This Phase Ib/II, multicenter, open-label trial investigates the antitumor activity of MSC2156119J + gefitinib in pts with MET+ advanced EGFRm+ NSCLC (NCT01982955). Methods: Primary objectives are 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 include safety, pharmacokinetics, and antitumor activity of MSC2156119J (PFS per independent read, overall survival, objective response, and disease control). Adults with advanced NSCLC with activating EGFR mutation, ECOG status 0–1, and resistance on 1st-line gefitinib (Phase II only) are recruited in mainland China, South Korea, Taiwan, and other Asian countries. Patients must have confirmed MET+ status, defined as either strong or moderate protein overexpression by immunohistochemistry, or MET gene amplification by in situ hybridization. Main exclusion criteria: life expectancy <3 mo, or prior EGFR targeting therapy other than gefitinib (Phase II only). For the Phase Ib part (3+3 design), 15–18 pts are planned to receive 300 or 500 mg MSC2156119J p.o. + 250 mg gefitinib p.o./d (21-d cycle); for the Phase II part, up to 200 pts are planned to be enrolled into 2 predefined subgroups according to their T790M mutation status and subsequently randomized 1:1 to RP2D MSC2156119J p.o. + 250 mg gefitinib p.o./d or 500 mg/m2 pemetrexed i.v. + 75 mg/m2 cisplatin i.v. on day 1 (max. of six 21-d cycles). Enrollment for Phase Ib began on Dec 23, 2013. Clinical trial information: NCT01982955.