ASCO GU 2020: Enfortumab Vedotin Plus Pembrolizumab for Locally Advanced or Metastatic Urothelial Carcinoma - Preliminary Durability Results from Study EV-103

San Francisco, California (  Patients with metastatic urothelial cancer traditionally, have faced limited options. While platinum chemotherapy is the standard in the first line setting, many patients are ineligible. Previously, it has been shown that PD-1/PD-L1 inhibitors, demonstrate promising effectiness in this setting. Enfortumab vedotin (EV) is an antibody-drug conjugate that delivers the microtubule-disrupting agent MMAE to cells expressing Nectin-4. This receptor is highly expressed in urothelial cells and in previous studies, EV has shown activity in previously treated metastatic patients.

Last year at ESMO, result regarding preliminary data on EV+ pembrolizumab in this setting was presented. Today, Dr. Rosenberg presented preliminary durability data, as well as, an update to the safety profile. This multicohort study (NCT03288545) evaluated the safety and efficacy of EV + pembrolizumab in cis-ineligible patients that had not received prior therapy. The primary endpoint was safety and tolerability. Secondary objectives included determination of recommended dose, overall response, progression free survival, and duration of response. 

The initial results were promising, with a confirmed investigator-assessed objective response rate of 73.3% (95% CI, 58.1, 85.4), this included a 15.6% complete response rate. The drug remained effect regardless of PD-L1 status. For patients with available PD-L1 information, ORR 78.6%  and 63.2%, respectively in high (11/14) and low (12/19) expression patients.


Furthermore, while these are preliminary results, the response appears to be durable with 55% of responders having an ongoing response at the time of this presentation.


These treatment benefits were realized with relatively few serious treatment related side effects. The most adverse events (AE) were fatigue (58%, 11% ≥G3), alopecia (53%), and peripheral sensory neuropathy (53%, 4% ≥G3). However, one patient in the study did die due to multiple organ failure.

To conclude the talk, Dr. Rosenberg reminded the audience of the real need for good treatment options in the cisplatin ineleigble patient and that these preliminary results are exciting for this community. He did caution, that the data is still young and continued maturation is needed. However, he highlighted the groups planes to investigate wider indications, launching a Phase III trial comparing the combination against gemcitabine/platinum in the first line setting. 

Presented by: Jonathan E. Rosenberg, MD, Memorial Sloan Kettering Cancer Center, New York City, New York, USA

Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

email news signup