Background: Gastric/esophageal cancers have moderate/high Nectin-4 expression. EV is a Nectin-4–directed antibody–drug conjugate approved for use in locally advanced or metastatic (la/m) urothelial carcinoma. We report antitumor activity and safety of EV monotherapy in esophageal and/or gastric cancer in EV-202 (NCT04225117). Methods: This open-label, multicohort, phase 2 study enrolled adults with la/m solid tumors and ECOG performance status 0–1. In the esophageal squamous cell carcinoma (ESCC) and gastric/esophageal adenocarcinoma (GEA; gastric cancer, gastroesophageal junction/esophageal adenocarcinoma) cohorts, patients (pts) had prior treatment with 1 platinum-based and ≤2 lines of cytotoxic therapy in the la/m setting and disease not amenable to curative intent. Inclusion required prior HER2-directed therapy if HER2-positive and prior PD-1/L1 inhibitor. Nectin-4 expression was assessed retrospectively. Pts received EV 1.25 mg/kg intravenously on days 1, 8, and 15 per 28-day cycle. Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1; ≥7 out of 40 responders are needed to conclude promising antitumor activity. Secondary endpoints were investigator-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) per RECIST v1.1; overall survival (OS); and safety/tolerability. Results: Of the 44 (as of June 2, 2023) and 42 pts (as of Mar 3, 2023) in the ESCC and GEA cohorts, respectively, median age was 66 and 62 y, 82% and 71% of pts were male, and 68% and 69% had ≥2 prior lines of systemic therapy in the metastatic setting. Efficacy data are shown in the table. Efficacy was generally better in pts with <3 (n=22) vs ≥3 (n=21) prior therapy lines in the ESCC cohort. Common treatment-related adverse events (TRAEs) were pruritus (n=12, 27%), maculopapular rash (n=12, 27%), and dysgeusia (n=11, 25%) for ESCC and pruritus (n=16, 38%), alopecia (n=15, 36%), and dysgeusia (n=13, 31%) for GEA. Grade ≥3 TRAEs (>1 pt) were hypercalcemia, hyperglycemia, maculopapular rash, and decreased neutrophil count (each n=2, 5%) for ESCC and maculopapular rash (n=3, 7%), decreased neutrophil count (n=2, 5%), and hyperglycemia (n=2, 5%) for GEA. For ESCC and GEA, respectively, TRAEs of special interest included skin reactions (n=27, 61%; n=23, 55%), peripheral neuropathy (n=9, 20%; n=7, 17%), and hyperglycemia (n=3, 7%; n=3, 7%). Conclusions: In pts with pretreated gastric/esophageal cancers, EV demonstrated safety consistent with the known profile of EV. Promising antitumor activity was observed in pts with ESCC. Clinical trial information: NCT04225117.

Values are median unless otherwise noted. NE, not estimable.

*Assessed in pts with confirmed response (ESCC: N=8; GEA: N=4).