Enfortumab Vedotin (EV) in the Previously Treated Advanced Head and Neck Cancer (HNC) Cohort of EV-202

Purpose/Objective(s)

The prognosis of patients (pts) with recurrent/metastatic head and neck squamous cell carcinoma (SCC) is poor (median overall survival [OS] 10–13 mo), and effective treatments are needed. The cell-adhesion molecule Nectin-4 is expressed in a majority of HNCs. EV is a Nectin-4–directed antibody–drug conjugate approved as monotherapy in previously treated locally advanced or metastatic (la/m) urothelial carcinoma (UC) and, in the US, with pembrolizumab for previously untreated la/mUC ineligible for cisplatin. EV was evaluated in previously treated HNC in EV-202 (NCT04225117).

Materials/Methods

In this open-label phase 2 study, pts with la/m solid tumors enrolled in tumor-specific cohorts. In this cohort, pts had HNC not amenable to curative-intent treatment, radiographic progression on/after the last regimen, progression/relapse/discontinuation for toxicity after 1 platinum-based therapy for la/m disease, and ≤2 lines of cytotoxic therapy in the la/m setting. Pts had received prior programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor unless contraindicated. Pts received intravenous EV 1.25 mg/kg on days 1, 8, and 15 of each 28-d cycle (C) until disease progression or discontinuation criteria were met. Primary endpoint was confirmed objective response rate (ORR) per investigator assessment. Secondary endpoints were duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) per investigator assessment; OS; and safety/tolerability. Exploratory endpoints included immunogenicity, pharmacokinetic parameters, and pt-reported outcomes.

Results

As of April 11, 2022, 46 pts were enrolled; median follow-up was 9.3 mo. Median age was 65 y, 87.0% of pts were men, and 52.2% had ≥3 prior lines of systemic therapy in the metastatic setting. Forty-five pts had SCC; 1 had adenocarcinoma. Confirmed ORR was 23.9%; DCR was 56.5%. Median time to response was 1.7 mo. Median DOR was not estimable. Median PFS and OS were 3.9 and 6.0 mo, respectively. Common treatment-related adverse events (TRAEs) were alopecia (28.3%), fatigue (26.1%), and peripheral sensory neuropathy (23.9%). Grade ≥3 TRAEs occurring in >1 pt were anemia and decreased neutrophil count (both n=2). TRAEs of special interest were skin reactions (45.7%), peripheral neuropathy (32.6%), dry eye (6.5%), and hyperglycemia (4.3%). No antitherapeutic antibodies against EV were detected. Serum EV decreased substantially from end-of-infusion concentrations before subsequent doses in C1, while plasma concentration of free monomethyl auristatin E (drug component of EV) remained high between days 1 and 15 of C1. Median global pain assessment score was 4/10 at baseline, with numeric reduction in scores (indicating pain improvement) in C3 and beyond.

Conclusion

EV demonstrated antitumor activity with manageable AEs in pts with heavily pretreated HNC post-platinum and PD-1/L1 inhibitor.