Abstract 1195: Prospective study for the identification of nivolumab biomarkers via analyses of pre-treatment plasma exosome mRNAs from head and neck cancer patients (BIONEXT)

Abstract

Abstract Nivolumab paved a new way in the treatment of recurrent or metastatic (RM) head and neck squamous cell carcinoma of (HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and as well provides a biological clue to develop effective therapies for a majority of non-survivors. Pre-treatment plasmas (N = 104) were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment naïve tumor and plasma samples (N = 20) were assayed to elucidate biological implications of the PEX mRNA signature. A combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely (P = 0.000124) distinguished non-survivors from >2-yr survivor (0% vs 57.7%) with a high hazard ratio (2.878; 95% confidence interval 1.639-5.055; P = 0.0002348). In paired samples, high PEX HLA-E mRNA (a non-survivor-predicting marker) reflected the increased HLA-E protein expression (P = 0.0191) and the dense population of tumor-infiltrating NK cells (P = 0.024) in the corresponding tumor. It is estimated that the effects of PD-1blockade is canceled by the HLA-E-NKG2A immune checkpoint in patients with high PEX HLA-E mRNA. The combination of NKG2A antibody (i.e., monalizumab) and nivolumab may be a promising strategy for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs. A candidate companion diagnostic of nivolumab that indicates a possible treatment option is identified. Citation Format: Muneyuki Masuda, Satoshi Toh, Mioko Matsuo, Masashi Sugasawa, Keisuke Yamazaki, Ueki Yushi, Torahiko Nakashima, Hideoki Uryu, Takeharu Ono, Tsutomu Ueda, Hirohito Umeno, Satoshi Kano, Kiyoaki Tsukahara. Prospective study for the identification of nivolumab biomarkers via analyses of pre-treatment plasma exosome mRNAs from head and neck cancer patients (BIONEXT) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1195.