Comprehensive Molecular Characterization Of Clinical Response In Ramucirumab-Treated Gastric Cancer Patients: Phase Ii Trial With Integrated Genomic Profiling.

4064 Background: The absence of tumor cells enables an enriched stromal environment to generate RNA signatures and through assembling genes involved in tumor stroma, four distinct stromal signatures that reflected biological processes such as signature vascular mature (VM), vascular mature/inflammatory (VMI), vascular immature/noninflammatory (VINI) and inflammatory alone (I) depending on mature of vasculature. We hypothesized that these stromal specific signatures may provide additional information to the pre-existing TCGA/ACRG subtypes when predicting response to anti-angiogenesis agent such as ramucirumab. Methods: We conducted a single-center phase II trial in which we treated 61 unselected patients with metastatic GC with ramucirumab plus paclitaxel as second line therapy and performed pre-planned integrated genomic profiling. Results: Sixty-two patients were enrolled in this study between May 2014 and June 2017. The cut-off date for treatment outcome analysis was January 2, 2019, at which time response evaluations were available for 57 patients with a median follow-up of 30.2months. In an intent-to-treat analysis cohort, there was no CR and 22 patients achieved confirmed PRs resulting in an ORR of 35.5% (95% CI: 23.6 – 47.4). The response rate to ramucirumab was considerably enriched in VM/VMI group (29.2%) (P = 0.0003) when compared to I ( < 10%) or VINI group ( < 10%). The strongest response defined by maximal response to ramucirumab was shown in GC patients with VM/VMI signatures. Of note, VM/VMI patients had prolonged duration of response to ramucirumab/paclitaxel demonstrating that these patients not only respond to ramucirumab but also had durable response. Conclusions: This is the first study to demonstrate a clinically robust correlation between stromal-based signature and response to anti-angiogenesis inhibitor in GC. Clinical trial information: 02628951.