Abstract LB090: Predictive genomic biomarkers for atezolizumab plus bevacizumab combination immunotherapy response in liver cancer: Insights from the IMbrave150 trial
Authors: Lee Ju-Seog , Yim Sun Young , Baek Seung-Woo , Lee Sung Hwan , Sohn BoHwa , Jeong Yun Seong , Kang Sanghee , Park Kena , Park Hyewon , Lee Sunyoung S. , Kaseb Ahmed O. , Kim Ji Hoon , Chu In-Sun 
Published: April 2024

Abstract
Introduction: Combination immunotherapy regimens, exemplified by atezolizumab plus bevacizumab or sintilimab paired with a bevacizumab biosimilar (IBI305), have become the established standard of care for individuals with inoperable hepatocellular carcinoma (HCC). Despite this advancement, the absence of clear predictive biomarkers and a comprehensive understanding of the mechanisms governing response and resistance to these combined therapies pose challenges. Our aim is to evaluate whether previously defined immune signature scores (ISS) from the TCGA pan-cancer study can identify HCC patients likely to derive enhanced benefit from the combination immunotherapy.
Methods: We applied ISS predictor to gene expression data from IMbrave150 clinical trial in which HCC patients were treated with atezolizumab plus bevacizumab or sorafenib and stratify the patients into responders and non-responders (cutoff of 0.5). The significance of the stratification was assessed by multiple statistical approaches using Kaplan-Meier plots, the log-rank test, chi-square tests, and cox regression analysis.
Results: In the IMBrave150 trial cohort, data on gene expression and outcomes were accessible for 247 patients who received atezolizumab plus bevacizumab, and 48 patients who received sorafenib. The high ISS demonstrated a significant association with enhanced PFS in the atezolizumab plus bevacizumab group (p=0.003), while no such association was observed in the sorafenib group (p=0.6). Similarly, in the high ISS subgroup, the combination therapy exhibited superior OS (p.0.001) and PFS (p=0.02) compared to sorafenib, but no discernible benefit was noted in the low ISS subgroup (both p&gt;0.7). The OS hazard ratio for the combination versus sorafenib was 0.26 (95% CI 0.14-0.51, p&lt;0.001) among high ISS patients, while it was not statistically significant in low ISS (HR 0.88, p=0.68). Interaction testing confirmed a notable interaction between ISS subtype and treatment benefit, particularly for OS (p=0.01). In the combination arm, the objective response rate was 45.6% in the high ISS group versus 22.8% in the low ISS group.
Conclusions: Our study suggests that ISS may serve as a promising predictive biomarker for enhanced therapeutic outcomes in patients undergoing combination immunotherapy for HCC. The identification of such markers is crucial for refining patient stratification and personalized treatment approaches, thereby advancing the effectiveness of current standard-of-care regimens in both early and advanced stage HCC. Further validation studies are warranted to solidify the clinical utility of ISS and its integration into the decision-making process for HCC immunotherapy.
Citation Format: Ju-Seog Lee, Sun Young Yim, Seung-Woo Baek, Sung Hwan Lee, BoHwa Sohn, Yun Seong Jeong, Sanghee Kang, Kena Park, Hyewon Park, Sunyoung S. Lee, Ahmed O. Kaseb, Ji Hoon Kim, In-Sun Chu. Predictive genomic biomarkers for atezolizumab plus bevacizumab combination immunotherapy response in liver cancer: Insights from the IMbrave150 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB090.