Abstract LB104: Tumor fraction as a predictive factor of outcome in patients referred for oncology early phase clinical trials: Analyses of two precision medicine studies
Authors: Belcaid Laila , Cousin Sophie , Bayle Arnaud , Alame Melissa , Rouleau Etienne , Blouin Laura , Lacroix Ludovic , Vasseur Damien , Brunet Maxime , Taleb Sofiane , Soubeyran Isabelle , Debien Veronique , Angeli Eurydice , Massard Christophe , Italiano Antoine 
Published: April 2024

Abstract
Modern phase I trials have shown considerable advancement, demonstrating encouraging response rates and subsequently raising the demand for participant enrollment. Despite these advances, there remains a significant challenge: approximately 15% of patients enrolled in these trials pass away within the first 90 days, and nearly half of them do not experience any therapeutic benefit. These statistics underscore the critical need for more effective strategies in selecting suitable patients for trial participation. One promising avenue is the use of circulating tumor DNA (ctDNA) measurements to estimate tumor fraction (TF), a method that has shown potential in prognosticating outcomes for patients with solid tumors. Nevertheless, the effectiveness of TF as an indicator for predicting the clinical benefits of systemic treatments in patients referred for early phase studies is yet to be conclusively determined Methods: We analyzed adult patients with advanced solid tumors included from December 2020 to December 2021 in two precision medicine studies: BIP (NCT02534649) and STING (NCT04932525). Comprehensive genomic profiling was conducted using the FDA approved 324-gene FoundationOne Liquid Cdx assay. TF was categorized as ≥10% or &lt;10%. Multivariate analysis incorporated established prognostic scores (Royal Marsden Hospital: RMH, Garrido-Laguna et al. 2012; and GRIm, Bigot et al., 2017) and their individual components (RMH: albumin, lactate dehydrogenase, number of metastatic sites; GRIm: neutrophil/lymphocyte ratio, lactate dehydrogenase, albumin). Results: A total of 1305 patients referred for early phase trials were evaluated: 871 in BIP and 434 in STING.The treatment regimens patients received post-TF assessment included: cytotoxic agents (BIP: 278 patients, 28.8%; STING: 106 patients, 24.4%), immunotherapy (BIP: 152 patients, 15.8%; STING: 76 patients, 17.5%), tyrosine kinase inhibitors (BIP: 126 patients, 13.1%; STING: 35 patients, 8.1%), hormonal therapy (BIP: 131 patients, 13.6%; STING: 9 patients, 2.1%), and various other therapies or combinations. High TF was significantly correlated with poorer objective response/stable disease rate, shorter progression-free survival (PFS), and lower overall survival (OS) in both studies. Multivariate analysis confirmed TF as an independent predictor of objective response, PFS, and OS, beyond the RMH and GRIm scores and their components. Conclusions: This is the first prospective analysis confirming that TF is a significant predictive marker of treatment efficacy in patients referred for early phase studies. Our findings suggest that TF could be a valuable tool in decision-making for phase I trial participation. Additionally, this research lays the groundwork for future exploration of TF in risk stratification of cancer patients in various clinical contexts.
Citation Format: Laila Belcaid, Sophie Cousin, Arnaud Bayle, Melissa Alame, Etienne Rouleau, Laura Blouin, Ludovic Lacroix, Damien Vasseur, Maxime Brunet, Sofiane Taleb, Isabelle Soubeyran, Veronique Debien, Eurydice Angeli, Christophe Massard, Antoine Italiano. Tumor fraction as a predictive factor of outcome in patients referred for oncology early phase clinical trials: Analyses of two precision medicine studies [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 LB104.