First-In-Human Study: Dose Expansion of E7130 in Urothelial Carcinoma and Squamous Cell Carcinoma of the Head and Neck.

The dose escalation part of the first-in-human study of E7130 in patients with advanced solid tumors determined the Recommended Phase 2 Dose (RP2D) of E7130 (480 μg/m2 Q3W). The dose expansion part (presented here) examined safety/preliminary efficacy in patients with squamous cell carcinoma of the head and neck (SCCHN) and urothelial carcinoma (UC). Patients ≥ 20 years of age with previously treated SCCHN/UC were treated at the RP2D. The primary objective was to characterize tolerability/safety. Secondary objectives included preliminary efficacy (including objective response rate [ORR], progression-free survival [PFS], and duration of response [DOR] by investigator per Response Evaluation Criteria In Solid Tumors version 1.1 [RECIST v1.1] and overall survival [OS]). Treatment-emergent adverse events (TEAEs) were recorded. In patients with SCCHN, tissue biomarker analyses were performed. Kaplan-Meier method was used to estimate PFS, DOR, and OS. The Greenwood formula and log-log transformation were used to estimate 95% CIs. Eight patients (SCCHN, n = 2; UC, n = 6) were treated with the RP2D; 10 additional patients (SCCHN, n = 7; UC, n = 3) were treated at a reduced dose (410 μg/m2 Q3W). All patients had ≥ 1 TEAE; 66.7% had serious TEAEs. Patients with UC treated at the RP2D had an ORR of 66.7%; no other responses were observed. Median PFS/OS in patients with SCCHN treated at 480 μg/m2 were 2.8/7.7 months and at 410 μg/m2 were 3.5/5.0 months. Median PFS/OS in patients with UC treated at 480 μg/m2 were 6.6/10.7 months and at 410 μg/m2 were 2.6/11.9 months. Biomarker analyses indicated tumor microenvironment amelioration. Further evaluation is needed to optimize efficacy and safety of E7130 in patients with SCCHN and UC. Trial Registration: ClinicalTrials.gov identifier: NCT03444701.