Enfortumab vedotin and pembrolizumab as first-line treatment in recurrent or metastatic head and neck squamous cell carcinoma: A cohort of the EV-202 trial.
Authors: Yoshitaka Honma, Paul L. Swiecicki, Ari Joseph Rosenberg, Glenn J. Hanna, Justine Yang Bruce, Takao Fujisawa, Kei Muro, Jason B. Kaplan, Seema Rao Gorla, Shubin Liu, Changting Meng, Jessica Lyn Geiger
Journal: Journal of Clinical Oncology (2024)

TPS148 Background: Novel treatment strategies are needed to treat recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) given the poor durability of response and prognosis with standard therapy. In KEYNOTE-048, among patients with R/M HNSCC and PD-L1 combined positive score (CPS) ≥1, first-line (1L) treatment with pembrolizumab demonstrated a median overall survival (OS) of 12.3 months. Nectin-4 is widely expressed in a variety of solid tumors, including bladder cancers and HNSCC. Enfortumab vedotin (EV) is a Nectin-4–directed antibody–drug conjugate approved for use in previously treated (EV monotherapy) or 1L (EV + pembrolizumab) locally advanced or metastatic urothelial carcinoma (la/mUC). EV + pembrolizumab showed superior OS and progression-free survival (PFS) vs chemotherapy in 1L la/mUC. EV-202 is a multicenter, open-label, phase 2 study (NCT04225117) evaluating the efficacy and safety of EV in multiple tumor-specific cohorts. In the previously treated R/M head and neck cancer cohort, 11 of 46 patients (23.9%) had a confirmed objective response with EV monotherapy; median PFS was 3.9 months (Swiecicki P, et al. ASCO 2023. Poster #6017). We hypothesize that EV + pembrolizumab may demonstrate benefit as a 1L therapy in patients with R/M HNSCC and CPS ≥1. Methods: Patients in the R/M HNSCC cohort of EV-202 have histologically or cytologically confirmed HNSCC, an ECOG performance status 0 or 1, no prior systemic therapy administered in the R/M setting (with the exception of systemic therapy completed &gt;6 months prior if given as part of treatment for locally advanced disease), and CPS ≥1. A total of 40 patients are expected to be enrolled. An interim analysis will be conducted when 20 patients are evaluable for tumor response; 5 responders will be needed to proceed. Of 40 total patients, 14 must demonstrate response to claim promising antitumor activity. Patients will receive EV 1.25 mg/kg intravenously on days 1 and 8 and 200 mg of pembrolizumab intravenously on day 1 of each 21-day cycle until discontinuation, for reasons including disease progression or toxicity. Disease assessments will be performed 9 weeks from the first dose and every 6 weeks thereafter until disease progression, start of subsequent anticancer therapy, death, consent withdrawal, loss to follow-up, or study end, whichever occurs first. The primary endpoint is investigator-assessed, confirmed ORR per RECIST v1.1. Secondary endpoints include investigator-assessed duration of response, disease control rate, PFS, OS, and safety/tolerability. Analyses will also be evaluated per iRECIST. Exploratory analyses will include pharmacokinetics, immunogenicity, quality of life, and assessment of biomarkers that may correlate with treatment outcome, including Nectin-4 expression. Recruitment for this cohort began in November 2023 and is ongoing. Clinical trial information: NCT04225117 .