Abstract 36P
Background
Chromatin remodeler agents, including BET, HDAC6, PRMT5, LSD1 and EZH2 inhibitors, are emerging therapies that modulate epigenetic regulation and hold potential in treating solid and hematological malignancies. While promising, these agents necessitate evaluation of their toxicity profiles, particularly in heavily pretreated populations. This study aims to characterize the adverse event (AE) profiles associated with these agents in a phase I oncology unit.
Methods
We conducted a retrospective analysis of 112 patients treated with chromatin remodeler agents at the START - FJD Phase I Unit over a 9-year period (2015-2024). Patient demographics, treatment-related AEs (graded by CTCAE v5.0), and clinical outcomes were extracted from trial records. Each AE was counted one time and analyzed based on highest grade and drug attribution. Descriptive statistics were applied to summarize AE frequencies, grades, and treatment discontinuations.
Results
The cohort included 112 patients (46% male, 54% female, median age 64 years, range 20 - 86), with diverse advanced solid tumors, being the most prevalents GBM (26%), hepato-pancreato-biliary (18%) and adenoyd cistic carcinoma (10%), median prior treatments were 2 (range 0 - 8). Common AEs included gastrointestinal symptoms (25%), hematologic abnormalities (20%) and fatigue (11%). Grade 3-4 AEs were reported in 10% of patients, primarily thrombocytopenia (39%) and fatigue (14%). No grade 5 toxicities were observed. Treatment discontinuations due to AEs were rare (2%), with no recorded treatment-related fatalities. Most patients completed their planned treatment cycles, demonstrating the agents's tolerability.
Conclusions
Chromatin remodeler agents exhibit a favorable safety profile, with predominantly low-grade, manageable toxicities and minimal treatment discontinuations. These findings support the continued exploration of these agents in phase I trials, underscoring their potential as viable therapeutic options for patients with advanced solid tumors and hematological malignancies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
START-FJD Phase I Unit.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.