In the phase I EV-101 trial reported in the Journal of Clinical Oncology, Rosenberg et al found that the antibody-drug conjugate enfortumab vedotin had no maximum tolerated dose and was active in patients with metastatic urothelial carcinoma at the dose selected for phase II evaluation. The agent is a conjugate of a Nectin-4–directed antibody and a microtubule inhibitor.
The pivotal phase II EV-201 study supported the recent accelerated approval of the agent in patients with locally advanced or metastatic urothelial cancer who have previously received a programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.
In the dose-escalation/expansion study, 155 patients who had experienced disease progression on one prior chemotherapy regimen and/or PD-1/PD-L1 inhibitor received escalating doses of enfortumab vedotin up to 1.25 mg/kg on days 1, 8, and 15 of 28-day cycles. Overall, 96% of patients had received prior platinum-containing therapy and 72% had received PD-1/PD-L1 inhibitor therapy.
A maximum tolerated dose of enfortumab vedotin was not established, with the recommended phase II dose being identified as 1.25 mg/kg. Among the 112 patients treated at this dose, the most common treatment-related adverse events of any grade were fatigue (53%), alopecia (46%), decreased appetite (42%), and dysgeusia, nausea, and peripheral sensory neuropathy (38% each). The most common treatment-related grade ≥ 3 adverse events were maculopapular rash (3%) and fatigue (2%).
Among the 112 patients receiving the 1.25-mg/kg dose, the investigator-assessed confirmed objective response rate was 43% and median duration of response was 7.4 months. The response rate among 89 patients with prior PD-1/PD-L1 inhibitor therapy was 43% and median duration of response was 7.3 months.
Median overall survival was 12.3 months, with a 1-year rate of 52%. Median overall survival among the patients with prior PD-1/PD-L1 inhibitor therapy was 12.3 months.
The investigators concluded: “Single-agent [enfortumab vedotin] was generally well tolerated and provided clinically meaningful and durable responses in patients with [metastatic urothelial carcinoma]; survival data are encouraging…. These findings with [enfortumab vedotin] are especially encouraging for patients with [metastatic urothelial carcinoma] who had previously received an anti–PD-(L)1 therapy because there are no currently approved treatments. In addition, because of high Nectin-4 expression in urothelial tumor biopsy samples, … prescreening of Nectin-4 expression in tumor samples before [enfortumab vedotin] administration is not necessary.”
Daniel P. Petrylak, MD, Medical Oncology, Yale New Haven Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Astellas Pharma and Seattle Genetics. For full disclosures of all study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.