Clonal hematopoiesis (CH) associated mutations in patients with advanced solid tumors enrolled in phase I clinical trials.

Abstract

3056 Background: An increased number of CH associated mutations has been identified in patients (pts) with solid tumors. Their impact on pts outcomes remains unclear. This study aims to integrate molecular data and clinical characteristics of CH in pts enrolled phase I clinical trials. Methods: Data was collected retrospectively from medical records and molecular profile reports (Foundation One Liquid CDx Assay – 309 genes) performed before first study drug administration at the Drug Development department in Gustave Roussy (Villejuif, France) within the STING trial (NCT04932525). CH prevalence was assessed according to a variant allele frequency (VAF) threshold of 1% in epigenetic modifiers ( DNMT3A, TET2 and ASXL1). Results: From January 2021 to December 2022, 255 pts were enrolled in a phase I clinical trial and had a liquid biopsy. In total, 55% of patients were male with a median age of 62 years [24-86]. Most common tumor locations were gastrointestinal (27%), genitourinary (21%) and thorax (18%). Patients received a median of 2 prior lines of treatment before investigational study drug and CH assessment. At the end of the data cut off, 81% of pts discontinued phase I treatment mostly due to progression disease. Overall, 104 pts (41%) had at least 1 CH mutation in liquid biopsy at baseline with 55 pts (22%) at a VAF of ³ 1%. Mutation frequency was DNMT3A in 42% (n= 23), ASXL1 in 38% (n=21) and TET2 in 31% (n=17). Co-mutations were present in 26 patients, with the most frequent being DNMT3A + ASXL1. Median PFS and OS were 3.7 months (m) for CH group vs 3.5m for no-CH (p=0.3) and 24m CH vs 15m no-CH (p=0.5), respectively. Conclusions: CH is commonly found in pts with solid tumors treated in phase I trials, with a prevalence in our cohort of 22%. Most frequent mutated gene was DNMT3A. Prognostic implications of the impact of these mutations in patient´s outcomes remain to be elucidated and will be presented at the meeting.