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A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma
- Source :
- Cancer. 125(7)
- Publication Year :
- 2018
-
Abstract
- Background Glembatumumab vedotin is an antibody-drug conjugate that produced preliminary clinical activity against advanced melanoma in a phase 1 dose-escalation trial. The objective of the current study was to investigate further the antitumor activity of glembatumumab vedotin at the recommended phase 2 dose in heavily pretreated patients with melanoma. Methods This single-arm, phase 2 study enrolled patients with stage IV melanoma who were refractory to checkpoint inhibition and to B-raf proto-oncogene, serine/threonine kinase (BRAF)/mitogen-activated protein kinase kinase (MEK) inhibition (in the presence of a BRAF valine mutation at codon 600). Patients received 1.9 mg/kg glembatumumab vedotin intravenously every 3 weeks until they developed disease progression or intolerance. The primary endpoint was objective response rate (ORR), which was determined according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival (OS), safety, and clinical efficacy versus tumor glycoprotein NMB (gpNMB) expression. Tumor expression of gpNMB was assessed using immunohistochemistry. Results In total, 62 patients received treatment. The ORR was 11% and the median response duration was 6.0 months (95% confidence interval [CI], 4.1 months to not reached). The median PFS was 4.4 months (95% CI, 2.6-5.5 months), and the median OS was 9.0 months (95% CI, 6.1-11.7 months). For patients who developed rash during the first cycle versus those who did not, the ORR was 21% versus 7%, respectively, and there was an overall improvement in PFS (hazard ratio, 0.43; P = .013) and OS (hazard ratio, 0.43; P = .017). The most frequent adverse events were alopecia, neuropathy, rash, fatigue, and neutropenia. With one exception, all evaluable tumors were positive for gpNMB, and 46 of 59 tumors (76%) had 100% gpNMB-positive epithelial cells. Conclusions Glembatumumab vedotin had modest activity and an acceptable safety profile in patients with advanced melanoma who were refractory to checkpoint inhibitors and MEK/BRAF inhibition. Treatment-related rash may be associated with response.
- Subjects :
- Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
Antibody-drug conjugate
Immunoconjugates
Skin Neoplasms
Phases of clinical research
Neutropenia
Proto-Oncogene Mas
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Agents, Immunological
Internal medicine
Medicine
Humans
030212 general & internal medicine
Melanoma
Aged
Neoplasm Staging
Proportional Hazards Models
Aged, 80 and over
GPNMB
Membrane Glycoproteins
business.industry
Antibodies, Monoclonal
Middle Aged
medicine.disease
Rash
Progression-Free Survival
Treatment Outcome
chemistry
Response Evaluation Criteria in Solid Tumors
030220 oncology & carcinogenesis
Female
medicine.symptom
business
Glembatumumab vedotin
Subjects
Details
- ISSN :
- 10970142
- Volume :
- 125
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cancer
- Accession number :
- edsair.doi.dedup.....0a7f2e6f860a722e822a5755184715bd