A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma
Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Division of Medical Oncology and Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Division of Medical Oncology, Department of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
Division of Medical Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Department of Hematology and Oncology, Mayo Clinic Hospital, Florida, Jacksonville, FL 32224, USA
Division of Medical Oncology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Division of Hematology and Oncology, Department of Medicine, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03766, USA
Blueprint Medicines, Clinical Development, Cambridge, MA 02139, USA
Celldex Therapeutics, Inc., Hampton, NJ 08827, USA
Cancer Therapy Evaluation Program National Institute of Health (CTEP), Bethesda, MD 20892, USA
Department of Thoracic Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Author to whom correspondence should be addressed.
Hasanov and Rioth contributed equally to the manuscript.
Cancers 2020, 12(8), 2270; https://doi.org/10.3390/cancers12082270
Received: 7 July 2020 / Revised: 10 August 2020 / Accepted: 11 August 2020 / Published: 13 August 2020
(This article belongs to the Section Clinical Trials of Cancer)
Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease >100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5–5.6), and the median overall survival was 11.9 months (95% CI 9.0–16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release.