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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (12)
Paul L. Swiecicki
Emrullah Yilmaz
Johnson & Johnson, Raritan, NJ
Ari Joseph Rosenberg
Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL
Takao Fujisawa
Justine Yang Bruce
University of Wisconsin Carbone Cancer Center, Madison, WI
Changting Meng
Pfizer, Bothell, WA
Michele Wozniak
Paul L. Swiecicki, MDDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, Emrullah Yilmaz, MD, PhD, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, Ari Joseph Rosenberg, MDDepartment of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, Takao Fujisawa, MD, Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan, Justine Bruce, Yang MD, University of Wisconsin Carbone Cancer Center, Madison, WI, Changting Meng, MD, Pfizer, Bothell, WA, Michele, Wozniak PhD, Yongyun Zhao, PhD, Michael Mihm, PhD, Jason Kaplan, MD, and Seema Gorla, MD Astellas Pharma, Inc, Northbrook, IL and Jessica L. Geiger MD, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH
Yongyun Zhao
National Engineering Laboratory for Druggable Gene and Protein Screening, College of Life Science, Northeast Normal University
Michael Mihm
Astellas Pharma, Northbrook, IL
Jason Kaplan
Paul L. Swiecicki, MDDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, Emrullah Yilmaz, MD, PhD, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, Ari Joseph Rosenberg, MDDepartment of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, Takao Fujisawa, MD, Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan, Justine Bruce, Yang MD, University of Wisconsin Carbone Cancer Center, Madison, WI, Changting Meng, MD, Pfizer, Bothell, WA, Michele, Wozniak PhD, Yongyun Zhao, PhD, Michael Mihm, PhD, Jason Kaplan, MD, and Seema Gorla, MD Astellas Pharma, Inc, Northbrook, IL and Jessica L. Geiger MD, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH
Seema Gorla
Paul L. Swiecicki, MDDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, Emrullah Yilmaz, MD, PhD, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, Ari Joseph Rosenberg, MDDepartment of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, Takao Fujisawa, MD, Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan, Justine Bruce, Yang MD, University of Wisconsin Carbone Cancer Center, Madison, WI, Changting Meng, MD, Pfizer, Bothell, WA, Michele, Wozniak PhD, Yongyun Zhao, PhD, Michael Mihm, PhD, Jason Kaplan, MD, and Seema Gorla, MD Astellas Pharma, Inc, Northbrook, IL and Jessica L. Geiger MD, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH
Jessica L. Geiger
Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH