P1.01-87 A Phase 1b Study of TRC105 In Combination with Paclitaxel/Carboplatin and Bevacizumab in Patients with Stage 4 Non-Squamous Cell Lung Cancer

Abstract

liquid biopsy samples using targeted next-generation sequencing between 2014 and 2017 for EGFR exon20 mutations as well as other concurrent EGFR mutations in the same patient. Result: A total of 442 patients (3.4%) were found harboring 493 different EGFR exon20 variations, among which 49 patients (11%) carried more than one exon20 mutations. The frequencies of the most prevalent alterations were summarized in Table 1. 18% of these mutations have concurrent TKI-sensitive mutations L858R or exon19 deletion. In-frame deletion/insertions (delins or ins) and missense mutations were identified at a frequency of 53% and 47%, respectively. The short delins/ins occurred between 763w773 residues, while missense mutations dwelled at 768w820 residues, suggesting that these two types of alterations have their own manners for regulating EGFR kinase domain function. The most prevalent insertion is p.M766delinsMASV, occurred in 15.2% of all patients. Meanwhile, the diversity of inserted peptides at p.D770 and p.D771 positions is much higher than other positions with a total of 17 and 19 different insertion peptides composed of 1-5 amino acids, respectively. Missense mutations at S768 were detected in 20.4% of patients, but 60% of them were accompanied by mutations at G719. Conclusion: This is the largest cohort of Chinese lung cancers for studying EGFR exon 20 mutations, which should be informative for functional studies, the design of targeted drugs, and the testing for existing therapies.