A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced Adenocarcinoma of the stomach and Gastroesophageal junction

Background. The phase II YO28252 study (NCT01590719) examined first-line onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal junction. MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined. Patients and Methods. Patients were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles,followed by onartuzumab or placebo until disease progression. Coprimary endpoints were progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group and0.60 in the MET-positive population. Secondary end points were overall survival (OS), overall response rate (ORR), and safety. Results. Overall, 123patients were enrolled (n562onartuzumab, n 5 61 placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, respectively (HR, 1.08; 95% confidence interval [CI], 0.71–1.63; p 5 = 71). In the MET-positive population, median PFS was 5.95 versus 6.80months, onartuzumab versus placebo (HR, 1.38; 95% CI, 0.60–3.20; p5.45).Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64–1.75; p 5 =.83). In the MET-positive population, median OS was 8.51 versus 8.48 months for onartuzumab versus placebo, respectively (HR, 1.12, 95% CI, 0.45–2.78; p 5=.80). ORR was 60.5% for the onartuzumab group and 57.1%for placebo. Grade3–5adver see vents (AEs) wereseenin 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively. Conclusion. Theaddition of onartuzumab to mFOLFOX6 ingastric cancer did not improve efficacy in an unselected population orin a MET immunohistochemistry-positive population.