Dr. Rosenberg Discusses Enfortumab Vedotin in Urothelial Carcinoma

Jonathan E. Rosenberg, MD
Published: Wednesday, Jun 27, 2018



Jonathan E. Rosenberg, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma previously treated with an immune checkpoint inhibitor.

Enfortumab vedotin is an antibody drug conjugate that targets nectin-4, which is overexpressed in metastatic urothelial carcinoma. When this agent is infused into patients, it circulates throughout the body and is taken in by cells that express nectin-4. The vedotin is then released in the lysosome through cleavage by proteases, so that the cytotoxic kills the cancer cell through anti-microtubule activity.

Nectin-4 is also expressed in the skin at low levels, so skin toxicity can be an on-target toxicity of the drug, said Rosenberg. This provided the rationale for the phase I study that did an initial dose escalation, which identified the recommended phase II dose of 1.25 mg/kg. That dose is then administered once a week for 3 out of 4 weeks on a 28-day schedule.
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Jonathan E. Rosenberg, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma previously treated with an immune checkpoint inhibitor.

Enfortumab vedotin is an antibody drug conjugate that targets nectin-4, which is overexpressed in metastatic urothelial carcinoma. When this agent is infused into patients, it circulates throughout the body and is taken in by cells that express nectin-4. The vedotin is then released in the lysosome through cleavage by proteases, so that the cytotoxic kills the cancer cell through anti-microtubule activity.

Nectin-4 is also expressed in the skin at low levels, so skin toxicity can be an on-target toxicity of the drug, said Rosenberg. This provided the rationale for the phase I study that did an initial dose escalation, which identified the recommended phase II dose of 1.25 mg/kg. That dose is then administered once a week for 3 out of 4 weeks on a 28-day schedule.



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