Margetuximab (M) Plus Pembrolizumab (P) In Erbb2-Amplified Pd-L1+Gastroesophageal Adenocarcinoma (Gea) Post Trastuzumab (T).

4030Background: T + chemo is standard 1st line therapy (tx) for HER2+ GEA patients (pts). However, pts typically progress within 6-8 months, with up to 30% demonstrating loss of HER2 positivity. No HER2 targeted agents have been shown effective in the post-T setting. We report the results of M, a novel anti-HER2 monoclonal antibody + P (anti-PD-1) in HER2+ GEA pts in 2nd line post T progression and describe a biomarker enrichment strategy that compensates for tumor heterogeneity. Methods: HER2+ (pre-T testing) PD-L1-unselected GEA pts were enrolled. Endpoints include safety, objective response rate (ORR) by RECIST, and progression free survival (PFS). Exploratory endpoints include ERBB2 amplification (amp) status pre-M+P tx circulating-tumor DNA (ctDNA) by NGS (Guardant360) and PD-L1 on archival tissue by IHC (22C3 pharmDx). Results: As of 1/10/18, 60 pts were dosed in cohort expansion; 30 in North America (NA), 30 in Asia (A). Tx was well tolerated, with 13% of pts having TRAE ≥ grade 3, 3 drug-related S...