A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/8/2270 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Merve Hasanov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:29:29Z |
| format | Article |
| id | doaj.art-37878580db3741d8971218aed6c8824a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T17:29:29Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-37878580db3741d8971218aed6c8824a2023-11-20T10:03:42ZengMDPI AGCancers2072-66942020-08-01128227010.3390/cancers12082270A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal MelanomaMerve Hasanov0Matthew J. Rioth1Kari Kendra2Leonel Hernandez-Aya3Richard W. Joseph4Stephen Williamson5Sunandana Chandra6Keisuke Shirai7Christopher D. Turner8Karl Lewis9Elizabeth Crowley10Jeffrey Moscow11Brett Carter12Sapna Patel13Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADivision of Medical Oncology and Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADivision of Medical Oncology, Department of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USADivision 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, USADivision of Medical Oncology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USADivision of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADivision of Hematology and Oncology, Department of Medicine, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03766, USABlueprint Medicines, Clinical Development, Cambridge, MA 02139, USADivision of Medical Oncology and Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USACelldex Therapeutics, Inc., Hampton, NJ 08827, USACancer Therapy Evaluation Program National Institute of Health (CTEP), Bethesda, MD 20892, USADepartment of Thoracic Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAGlembatumumab 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.https://www.mdpi.com/2072-6694/12/8/2270uveal melanomaglembatumumab vedotinphase IIclinical trial |
| spellingShingle | 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 A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma Cancers uveal melanoma glembatumumab vedotin phase II clinical trial |
| title | A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma |
| title_full | A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma |
| title_fullStr | A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma |
| title_full_unstemmed | A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma |
| title_short | A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma |
| title_sort | phase ii study of glembatumumab vedotin for metastatic uveal melanoma |
| topic | uveal melanoma glembatumumab vedotin phase II clinical trial |
| url | https://www.mdpi.com/2072-6694/12/8/2270 |
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