Phase II Trial of Enfortumab Vedotin in Patients With Previously Treated Advanced Head and Neck Cancer

Abstract

Purpose: Despite advances in immunotherapy, unresectable recurrent/metastatic head and neck cancer (HNC) carries a poor prognosis, and effective treatments are needed. As nectin-4 is widely expressed in HNC, enfortumab vedotin (EV), a nectin-4-directed antibody-drug conjugate, was explored in HNC in EV-202 (ClinicalTrials.gov identifier: NCT04225117).

Methods: This open-label, multicohort, phase II study evaluated intravenous EV 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle. In the HNC cohort, eligible patients had recurrent/metastatic HNC and had received platinum-based therapy for locally advanced/metastatic disease and a PD-1/PD-L1 inhibitor. The primary end point was investigator-assessed confirmed objective response rate (ORR) per RECIST version 1.1. Secondary end points were investigator-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS); overall survival (OS); and safety.

Results: The primary analysis included 46 patients; all received EV (median follow-up, 9.3 months). Most patients (52.2%) had ≥3 previous lines of systemic therapy in the metastatic setting. Confirmed ORR was 23.9%, DCR was 56.5%, and median DOR was not reached (median DOR was 9.4 months at a later data cutoff [median follow-up, 11.3 months]). Median PFS and OS were 3.9 and 6.0 months, respectively. Treatment-related adverse events (TRAEs) occurring in >20% of patients were alopecia (28.3%), fatigue (26.1%), and peripheral sensory neuropathy (23.9%). Sixteen patients (34.8%) experienced grade ≥3 TRAEs; anemia and decreased neutrophil count occurred in ≥1 patient (both n = 2; 4.3%).

Conclusion: EV demonstrated antitumor activity in heavily pretreated HNC. Safety was consistent with the known safety profile of EV; no new safety signals were identified. These data support further evaluation of EV for advanced HNC not amenable to definitive local therapy.

FIG 1.

Patient flow diagram as of April 11, 2022. Only the primary reason for discontinuation was collected. ^aPatients could be excluded for more than one reason. ^bPatient also met an exclusion criterion (active CNS metastases). ^cOne patient also did not meet the inclusion criteria (la/m disease not amenable to curative-intent treatment). ^dExclusion criteria included the following cardiovascular conditions: unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months before the first dose of study drug. AE, adverse event; ECOG PS, Eastern Cooperative Oncology Group performance status; la/m, locally advanced or metastatic; PD, progressive disease.

FIG 2.

Efficacy per investigator assessment. (A) Best change from baseline in size of target lesion. (B) Outcomes in patients with confirmed responses (includes CR and PR). ^aA total of 39 patients with postbaseline tumor assessments were included; three patients were considered NE because their only postbaseline scan was performed before the protocol-specified minimum time of 49 days after the first dose. CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease.

FIG 3.

Kaplan-Meier plots of (A) DOR per investigator assessment, (B) PFS per investigator assessment, (C) OS, and (D) DOR per investigator assessment as of the July 15, 2022, data cutoff date. CR, complete response; DOR, duration of response; NR, not reached; OS, overall survival; PFS, progression-free survival; PR, partial response.