Phase 1 dose-escalation trial of talazoparib in combination with belinostat in select advanced solid tumors.

3043 Background: Inhibitors of histone deacetylase (HDACi) may synergize with poly (ADP-ribose) polymerase inhibitors (PARPi). This Phase 1 dose escalation trial tested the combination of the PARPi talazoparib and the HDACi belinostat. Methods: This open-label study was conducted with a combined dose escalation of talazoparib (0.75 mg-1 mg) and belinostat (500-1000 mg/m2) in subjects with advanced breast, ovarian, prostate and pancreatic cancers. Primary objectives were to identify the safety, tolerability, and recommended phase 2 dose (RP2D) of the combination. A TITE-CRM model was used for dose level assignment and identification of RP2D. Results: A total of 25 evaluable subjects were enrolled. Tumor types included breast cancer (10 subjects), ovarian cancer (5), prostate cancer (5), and pancreatic cancer (5). Treatment-related adverse events (AEs) included nausea (n = 8, 32%), fatigue (n = 8, 32%), thromboembolic events (n = 6, 24%), vomiting (n = 5, 25%), and anemia (n = 4, 16%). Treatment-related serious adverse events (SAEs) encompassed thromboembolic events (n = 4) and anemia (n = 1). Dose limiting toxicities (DLTs) occurred in 3 subjects including decreased white blood cell count, fatigue, anemia, and failure to thrive. Seven subjects experienced stable disease (SD), for a clinical benefit rate (CBR) of 28% (7/25); of those with SD, 6 were assigned to the highest dose (dose level 4) and 1 subject was assigned to dose level 3. Duration of enrollment ranged from 18-291 days. Conclusions: In subjects with select advanced solid tumors, talazoparib and belinostat combination therapy exhibits a favorable safety profile and manageable toxicity. Nausea and fatigue were the most common adverse events. Further studies are warranted to determine the efficacy of this combination. Clinical trial information: NCT04703920 .