Amgen announced results from an exploratory biomarker analysis evaluatingMET expression as a predictor of clinical response to rilotumumab (AMG 102)conducted on a previously reported Phase 2 study of rilotumumab in patientswith locally advanced or metastatic gastric or gastroesophageal cancer. Theanalysis showed that treatment with rilotumumab in combination withchemotherapy improved median overall survival (OS) in patients whose tumorsexhibited high MET protein expression.
In the Phase 2, three-arm trial, 121 patients were randomized 1:1:1 toreceive epirubicin, cisplatin and capecitabine (50mg/m2 IV Day 1, 60mg/m2 IVDay 1, 625mg/m2 twice daily orally Days 1-21, respectively) in combination withtwo different dose levels of rilotumumab (Arm A 15mg/kg every 3 weeks, n=40;Arm B 7.5mg/kg every 3 weeks, n=42) or placebo (Arm C, n=39). The primaryendpoint of the study was PFS. Secondary endpoints included OS, objectiveresponse rate (ORR) and safety. In the biomarker analysis, 90 patients wereevaluated for MET protein levels using an immunohistochemistry test.Twenty-seven patients from the rilotumumab treatment arms and 11 patients whoreceived placebo were found to have tumors with high MET expression, defined as>50% of tumor cells testing positive for the MET protein.
In this exploratory analysis, the addition of rilotumumab to chemotherapy inpatients with gastric tumors with high MET expression improved median OS from5.7 months to 11.1 months (HR=0.29, 95% CI, 0.11–0.76). Conversely, in patientswith gastric tumors with low MET expression, the addition of rilotumumab tochemotherapy was associated with a trend towards unfavorable OS (HR=1.84, 95%CI, 0.78–4.34).
Primary results of the study showed that the primary endpoint ofprogression-free survival (PFS) had a trend towards a better outcome withrilotumumab plus chemotherapy. The addition of rilotumumab to chemotherapyimproved median PFS from 4.2 months to 5.6 months (HR=0.64, 80% CI, 0.48–0.85).The secondary endpoint of OS also trended in favor of rilotumumab, withimproved median OS from 8.9 months to 11.1 months (HR=0.73, 80% CI, 0.53–1.01).
Rilotumumab is an investigational fully human monoclonal antibody designedto inhibit the hepatocyte growth factor/scatter factor (HGF/SF): MET pathway.
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