Abstract A61: Development of automated immunoassay to detect serum biomarkers predicting response to immune checkpoint inhibitors in NSCLC

Abstract Introduction: Immunotherapy with immune checkpoint inhibitors (ICI) is the standard of care for advanced non-small-cell lung cancer (NSCLC) without driver gene alterations. However, survival benefits with ICI are limited to a small subset of NSCLC patients, and particularly ICI combinations with cytotoxic agents produce serious physical and large financial toxicities. Tumor PD-L1 expression levels/proportion score (TPS) are universally used as predictive biomarkers in ICI monotherapy response and outcomes. However, PD-L1/TPS assays are imperfect because of low analytical validity and reproducibility due to the visual-scoring system by pathologists. Therefore, additional biomarkers are urgently needed to predict ICI therapy response and outcomes. Recently, we reported that serum antibodies (Abs) against NY-ESO-1 and XAGE1 cancer-testis antigens were probably useful biomarkers in the prediction of clinical benefits with anti-PD-1 monotherapy for NSCLC (J Thorac Oncol, 2019). Additionally, we developed a fully automated immunoassay system (HISCLTM) to measure the Abs easily and rapidly (Sakai Y, et al. Clin Chim Acta 2021). In this study, we retrospectively examined whether the Abs measured by HISCLTM predict the clinical benefits with ICI monotherapy for NSCLC.Patients and Methods: Sera were obtained from controls of non-malignant lung diseases (n=75) and healthy subjects (n=100), and advanced NSCLC patients (n=263) to to determine a cutoff value in HISCLTM. In NSCLC patients analyzed here (n=78), sera were obtained before anti-PD-1 monotherapy with nivolumab in second-line or later settings. The serum NY-ESO-1/XAGE1 Abs were measured by HISCLTM, and we examined the relationships between the Abs levels, objective response rate (ORR), progression free survival (PFS), and overall survival (OS) after nivolumab monotherapy.Results: NY-ESO-1/XAGE1 Abs levels in NSCLC patients (n=263) were significantly higher than those in the controls (n=175). A cutoff value was determined as the Abs level of 10 SU/mL, calculated from the Abs values in the controls. The Abs (≥ 10 SU/mL) were detected in 21/78 (27%) of the NSCLC patients treated with nivolumab, and one patient had both NY-ESO-1 and XAGE1 Ab. An ORR was 62%, 16%, and 29% in the Abs-positives, the Abs-negatives, and overall, respectively. The Abs levels in responders were significantly higher than those in non-responders. The NSCLC patients with high-Abs values (≥ 10 SU/mL) had significantly better survivals with nivolumab monotherapy than those with low-Abs (PFS, HR 0.51, 95%CI 0.31-0.83, p < 0.01; OS, HR 0.51, 95%CI 0.31-0.84, p < 0.01). Interestingly, a few NSCLC patients with both high-Abs and driver genes responded well to nivolumab.Conclusions: Serum NY-ESO-1/XAGE1 Abs measured by HISCLTM are potential biomarkers that predict clinical benefits with anti-PD-1 monotherapy for NSCLC, even including driver genes. These findings warrant further biomarker studies using NY-ESO-1/XAGE1 Abs in clinical trial and practice of NSCLC immunotherapy. Citation Format: Kanako Sakaeda, Koji Kurose, Minoru Fukuda, Nanae Sugasaki, Akitoshi Kinoshita, Takashi Kitazaki, Masaaki Fukuda, Takeshi Masuda, Noboru Hattori, Yusuke Atarashi, Yumiko Sakai, Yasuhiro Irino, Mami Yamaki, Toshiyuki Sato, Hiroshi Mukae, Toru Oga, Mikio Oka. Development of automated immunoassay to detect serum biomarkers predicting response to immune checkpoint inhibitors in NSCLC [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A61.