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A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma.

Publication ,  Journal Article
Ott, PA; Pavlick, AC; Johnson, DB; Hart, LL; Infante, JR; Luke, JJ; Lutzky, J; Rothschild, NE; Spitler, LE; Cowey, CL; Alizadeh, AR; He, Y ...
Published in: Cancer
April 1, 2019

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.

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Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

April 1, 2019

Volume

125

Issue

7

Start / End Page

1113 / 1123

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Skin Neoplasms
  • Proto-Oncogene Mas
  • Proportional Hazards Models
  • Progression-Free Survival
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Middle Aged
  • Membrane Glycoproteins
  • Melanoma
 

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Ott, P. A., Pavlick, A. C., Johnson, D. B., Hart, L. L., Infante, J. R., Luke, J. J., … Hamid, O. (2019). A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma. Cancer, 125(7), 1113–1123. https://doi.org/10.1002/cncr.31892
Ott, Patrick A., Anna C. Pavlick, Douglas B. Johnson, Lowell L. Hart, Jeffrey R. Infante, Jason J. Luke, Jose Lutzky, et al. “A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma.Cancer 125, no. 7 (April 1, 2019): 1113–23. https://doi.org/10.1002/cncr.31892.
Ott PA, Pavlick AC, Johnson DB, Hart LL, Infante JR, Luke JJ, et al. A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma. Cancer. 2019 Apr 1;125(7):1113–23.
Ott, Patrick A., et al. “A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma.Cancer, vol. 125, no. 7, Apr. 2019, pp. 1113–23. Pubmed, doi:10.1002/cncr.31892.
Ott PA, Pavlick AC, Johnson DB, Hart LL, Infante JR, Luke JJ, Lutzky J, Rothschild NE, Spitler LE, Cowey CL, Alizadeh AR, Salama AK, He Y, Hawthorne TR, Bagley RG, Zhang J, Turner CD, Hamid O. A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma. Cancer. 2019 Apr 1;125(7):1113–1123.
Journal cover image

Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

April 1, 2019

Volume

125

Issue

7

Start / End Page

1113 / 1123

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Skin Neoplasms
  • Proto-Oncogene Mas
  • Proportional Hazards Models
  • Progression-Free Survival
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Middle Aged
  • Membrane Glycoproteins
  • Melanoma