A phase ii study of glembatumumab vedotin for metastatic uveal melanoma

Merve Hasanov, Matthew J. Rioth, Kari Kendra, Leonel Hernandez-Aya, Richard W. Joseph, Stephen Williamson, Sunandana Chandra, Keisuke Shirai, Christopher D. Turner, Karl Lewis, Elizabeth Crowley, Jeffrey Moscow, Brett Carter, Sapna Patel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number2270
Pages (from-to)1-12
Number of pages12
JournalCancers
Volume12
Issue number8
DOIs
StatePublished - Aug 2020

Keywords

  • Clinical trial
  • Glembatumumab vedotin
  • Phase II
  • Uveal melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Hasanov, M., Rioth, M. J., Kendra, K., Hernandez-Aya, L., Joseph, R. W., Williamson, S., Chandra, S., Shirai, K., Turner, C. D., Lewis, K., Crowley, E., Moscow, J., Carter, B., & Patel, S. (2020). A phase ii study of glembatumumab vedotin for metastatic uveal melanoma. Cancers, 12(8), 1-12. [2270]. https://doi.org/10.3390/cancers12082270