A randomized, controlled, open label phase II study of erlotinib (E) with or without the MET antibody emibetuzumab (Emi) as first-line treatment for EGFRmt non-small cell lung cancer (NSCLC) patients who have disease control after an 8-week lead-in treatment with erlotinib.

Abstract

9019 Background: MET expression is a mechanism of resistance to EGFR inhibition in EGFRmt NSCLC and correlated with poor prognosis. Emi (LY2875358) is a humanized IgG4 monoclonal bivalent MET antibody that blocks ligand dependent and independent HGF/MET signaling. This Phase 2 study compared the clinical activity of Emi + E versus single agent E in 1st line EGFRmt metastatic NSCLC. Methods: Stage IV, EGFRmt NSCLC pts with disease control following an 8-week lead-in E (150 mg PO QD) treatment were randomized 1:1 to receive Emi (750 mg IV Q2W) + E or E alone. Pts were stratified by ECOG PS, ethnicity, MET expression status, and response at the end of the lead-in. The primary endpoint was PFS from randomization. Additional endpoints included safety, OS, PK, and exploratory analysis of MET-expressing populations. Results: Out of181 pts enrolled, 141 pts were randomized (Emi+E: 71; E: 70). In the ITT population, median PFS for EMI+E was 9.3 months (m) compared with 9.5 m for E (HR = 0.89: 90% CI 0.64-1.23; p = 0.534). Exploratory analysis of MET-high expressing pts (MET 3+ expression in ≥90% of tumor cells; n = 24 pts) showed a 15.3 m improvement in PFS (EMI+E: 20.7 m; E: 5.4 m [HR: 0.39; 90% CI: 0.17-0.91]). No difference in PFS was observed in the complementary population (HR: 1.1 [90% CI: 0.7-1.7]). Similar frequencies of related AEs were reported for both treatment arms. Drug-related TEAEs that were more frequent ( > 10%) for Emi+E were peripheral edema and fatigue (all grade 1 or 2). Emi serum concentrations were consistent with previously obtained PK results, and no apparent exposure-response was observed. Median OS in the ITT population was not achieved (NA) for either arm. In MET-high expressing pts, median OS was 20.6 m for E (90% CI: 8.87, NA) whereas it was not achieved for Emi+E (90% CI: NA, NA). Conclusions: No statistically significant difference in PFS was noted in the ITT population.Exploratory analysis confirmed that high MET expression is a negative prognostic marker for pts treated with E and indicated that these pts may receive clinically meaningful benefit from Emi+E. Clinical trial information: NCT01897480.