Glembatumumab Vedotin Shows Promising Response in Advanced Melanoma

A phase two study of the antibody-drug conjugate (ADC) glembatumumab vedotin (GV) has resulted in promising outcomes for patients with refractory advanced melanoma.

The single-arm, open-label, phase two study was conducted by the Dana-Farber Cancer Institute’s Melanoma Centre. It assessed the efficacy and safety of GV monotherapy in patients with measurable, unresectable stage three or four melanoma who had received cytotoxic chemotherapy, checkpoint inhibitor and, if the tumour had a BRAF V600 mutation, BRAF/MEK inhibitor.

GV contains a fully human IgG2 antibody to glycoprotein NMB (gpNMB), an internalisable, transmembrane glycoprotein overexpressed in multiple tumour types, including melanoma. High tumour gpNMB expression is associated with a worse prognosis. The ADC delivers monomethyl auristatin E, a potential antimitotic agent to gpNMB-expressing tumour cells. After internalisation of the conjugate, the linker is cleaved, releasing free MMAE within those tumour cells, and causing tubulin inhibition and cell death.

Most patients exhibited adverse side-effects including neuropathy, alopecia, rash, fatigue, neutropenia, nausea, decreased appetite, pruritus, and diarrhea. The presence of a high rash in cycle one is thought to be a predictive marker of response.

The study concluded that GV showed encouraging anti-tumour activity in patients with poor prognosis, CPI-refractory, advanced melanoma. Most patients experienced disease control for at least three months, with a tolerable safety profile.

 

Source: Targeted Oncology

Lederman, L. (June 13, 2017) Glembatumumab Vedotin Shows Promising Overall Response in Advanced Melanoma. Targeted Oncology.


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