Enfortumab Vedotin Monotherapy Yields Durable Responses in Metastatic Urothelial Cancer

Enfortumab vedotin monotherapy has demonstrated meaningful and durable responses in a phase 1 clinical trial of patients with metastatic urothelial carcinoma (mUC; J Clin Oncol. 2020 Feb 7. Epub ahead of print).

“Currently, a high unmet medical need exists for effective and tolerable treatments in patients with [mUC],” explained Jonathan Rosenberg, MD, Memorial Sloan Kettering Cancer Center, New York, and colleagues, who sought to evaluate the safety, tolerability, and antitumor activity of enfortumab vedotin in this setting.

Thus, Dr Rosenberg et al carried out the EV-101 dose escalation/expansion study of 155 heavily pretreated patients with mUC that progressed with ≥1 previous chemotherapy regimens and/or PD-1/PD-L1 inhibitors. Of note, 96% of patients in the study had previously received platinum-based chemotherapy and 29% had undergone ≥3 prior lines of therapy.

These patients were given escalating doses of enfortumab vedotin up to 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle. The primary end points of EV-101 were the safety, tolerability, and pharmacokinetics of the trial drug; a secondary end point was antitumor activity.

Although the investigators did not determine the maximum tolerated dose of enfortumab vedotin, they did identify a recommended phase 2 dose of 1.25 mg/kg. The most common treatment-related adverse events reported with the study drug were grade 1-2, and included rash, peripheral neuropathy, fatigue, alopecia, and nausea.

Ultimately, 112 patients with mUC received monotherapy with enfortumab vedotin 1.25 mg/kg. These patients had an investigator-assessed confirmed objective response rate (ORR) of 43%, and responses lasting 7.4 months.

The median overall survival (OS) was 12.3 months, and the 1-year OS was approximately 52%. The findings yielded similar ORR and estimated median OS rates in patients aged ≥75 years with and without prior anti–PD-1 or anti–PD-L1 therapy, liver metastases, or upper-tract disease.

“Single-agent EV [enfortumab vedotin] was generally well tolerated and provided clinically meaningful and durable responses in patients with mUC; survival data are encouraging,” Dr Rosenberg and colleagues said.

“A pivotal phase II and a confirmatory phase III study are ongoing,” they concluded.—Hina M. Porcelli