First‐In‐Human Study: Dose Expansion of <scp>E7130</scp> in Urothelial Carcinoma and Squamous Cell Carcinoma of the Head and Neck

ABSTRACT 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/m 2 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/m 2 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/m 2 were 2.8/7.7 months and at 410 μg/m 2 were 3.5/5.0 months. Median PFS/OS in patients with UC treated at 480 μg/m 2 were 6.6/10.7 months and at 410 μg/m 2 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