Abstract 2187: Circulating tumor DNA (ctDNA) gene sequencing results from prospective screening of patients with newly diagnosed metastatic gastric and gastroesophageal adenocarcinoma (GEA) for the bemarituzumab FIGHT randomized trial using a plasma NGS assay
Authors: Catenacci Daniel , Kang Yoon-Koo , Enzinger Peter , Cardellino Giovanni G. , Sanchez Raquel Guardeno , Xu Aaron Q. , Tappe Allie , Sun Michelle Y. , Mitra Siddhartha , Murphy Derek , Misner Ian , Smith Steven , Wainberg Zev 
Published: July 2021

Abstract
Background: Metastatic GEA is a molecularly heterogeneous disease with limited therapeutic options. It is the third most common cause of cancer death globally. Targeted therapies against HER2 positive and microsatellite instability-high (MSI-H) GEA have improved overall survival. There has not been a prospective evaluation of the prevalence of potentially actionable molecular targets in a global population with newly diagnosed advanced-stage GEA.
Methods: As part of the global FIGHT study of bemarituzumab (NCT03694522), patients with newly diagnosed advanced stage GEA that was not known to be HER2 positive were screened using the PGDx elioTM Plasma Resolve Investigation Use Only assay. This next generation sequencing (NGS) hybrid-capture assay was developed to include coding and select noncoding regions of 33 cancer-related genes. Circulating cell free DNA (cfDNA) extracted from plasma samples was used as input. FGFR2-amplification positive clinical samples were identified in a primary report for enrollment in the trial. Variant calls for translocations, amplifications and SNVs/indels were reported for informational use only.
Results: Of the 721 samples submitted for analyses, 661 had sufficient cfDNA to proceed with the assay, 51 samples failed to generate sufficient sequencing data to be interpreted based upon quality cutoffs. Of the 610 remaining samples 5% were amplified for FGFR2. Of these 610 samples, 496 (82%) individual patient samples were tested for additional molecular changes with 29 failing to generate sufficient sequencing data; leaving 467 patient samples with evaluable data. 81% of patients had at least one gene aberration. Of the 8 genes evaluated for amplification, the most common to least commonly amplified were MYC (10%), EGFR (7%), ERBB2 (7%), MET (7%), FGFR2 (5%), CCND1 (4%), and CD274 (1%). No KIT amplification was reported. The most frequently mutated genes among the 33 examined were p53, ARID1A, PIK3CA, BRCA2, KRAS, CDH1, APC, ATM, BRCA1 and FGFR2. Other identified mutations in genes of interest for which targeted therapies exist include mutations in NTRK1 (n=8) and ROS1 (n=15). Screening for 5 gene fusions identified fusions in 15 patients with 12 involving FGFR2.
Conclusions: This is the largest prospective global survey of genetic abnormalities using targeted ctDNA testing in newly-diagnosed advanced-stage GEA in patients whose tumors were not known to be HER2 positive. Using a multi-gene panel NGS approach to identify patients with FGFR2 amplification by ctDNA, other potentially clinically actionable genetic abnormalities were identified.
Citation Format: Daniel Catenacci, Yoon-Koo Kang, Peter Enzinger, Giovanni G. Cardellino, Raquel Guardeno Sanchez, Aaron Q. Xu, Allie Tappe, Michelle Y. Sun, Siddhartha Mitra, Derek Murphy, Ian Misner, Steven Smith, Zev Wainberg. Circulating tumor DNA (ctDNA) gene sequencing results from prospective screening of patients with newly diagnosed metastatic gastric and gastroesophageal adenocarcinoma (GEA) for the bemarituzumab FIGHT randomized trial using a plasma NGS assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2187.