Abstract B015: Tumor fraction as a predictive factor of outcome of patients referred for oncology early phase clinical trials: Analysis of the STING precision medicine study

Abstract

Abstract Background The quantification of ctDNA shed by measuring tumor fraction (TF) has been associated with prognosis in solid tumors pts. However, whether TF can be also predictive of clinical benefit of systemic treatments in patients referred for early phase studies remain unknown. Methods: All consecutive adult pts with an advanced solid tumor referred to the Early Phase Trials Department of Gustave Roussy( Villejuif France) between December 2020 and December 2021 and enrolled in the precision medicine study STING (NCT04932525, sponsor: Institut Gustave Roussy, Villejuif, France) were analyzed. All pts underwent comprehensive genomic profiling with the 324-gene FoundationOne. TF was analyzed as a binary variable, indicating whether a specimen had TF ≥10% or TF <10%. Response to treatment was assessed as per RECIST criteria. Multivariate analysis included previously validated prognostic scores: the Royal Marsden Hospital (albumin, LDH, number of metastatic sites) and the GRIm (LDH, neutrophil/lymphocyte ratio (NLR), albumin) scores as well as their individual components. Results: 947 patients entered the study. High TF was associated with significantly worse overall survival (OS) (HR:2.52 [CI95%: 2.06 - 3.08, p<0.001] independently of the RMH and GRIM scores as well as their individual components. 409 pts received a systemic treatment following ctDNA profiling (Immuno-oncology agent: 146 patients, non-IO: 254 patients)The treatment was investigational for 200 patients. The most frequent tumor types were non-small cell lung cancer (n=85), prostate cancer (n=49), colorectal cancer (n=33). High TF was significantly associated with worse objective response/stable disease rate (37.8% vs 53.8%, p=0.006), PFS (2.1 vs 3.9 months, p<0.001) and OS (7.1 vs 18.6 months, p<0.001) . Conclusions: Besides its prognostic value, TF is predictive of outcome on systemic therapy in patients referred for early phase studies. This parameter can be used for informed decision making for patients before participating in phase 1 trials. Citation Format: Laila Belcaid, Arnaud Bayle, Kilian Trin, Mihaela Aldea, Damien Vasseur, Madona Sakkal, Yohann Loriot, Antoine Hollebecque, Santiago Ponce, Antoine Italiano. Tumor fraction as a predictive factor of outcome of patients referred for oncology early phase clinical trials: Analysis of the STING precision medicine study [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B015.