Investigational Drug Shows Promise in Patients with Metastatic Urothelial Cancer

Enfortumab vedotin may be a potential novel therapy for patients with locally advanced or metastatic urothelial cancer, according to updated phase 1 study findings presented during the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

Urothelial cancer is the most common type of bladder cancer, according to the American Cancer Society. This year, more than 81,000 people in the United States will receive a bladder cancer diagnosis. Therefore, patients are in need of novel therapies.

“Many patients with locally advanced or metastatic urothelial cancer previously treated with checkpoint inhibitors have a poor prognosis and limited subsequent treatment options,” Jonathan E. Rosenberg, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, said in a press release. “Data from the ongoing study support the potential of enfortumab vedotin in locally advanced or metastatic urothelial cancer, based on the objective response rate and preliminary estimates of survival.”

In total 155 patients (median age, 67 years) were enrolled in the trial, of which 112 were evaluable. The primary tumor site was the bladder, however, some patients had liver metastases. The researchers’ primary objective was tolerability.

Patients received a 30-minute infusion of enfortumab vedotin on days 1, 8 and 15 of each 28-day cycle. Nearly two-thirds (63 percent) of patients received two or more prior therapies in the metastatic setting — the majority with a checkpoint inhibitor. And, 81 percent received prior platinum chemotherapy.

The investigational antibody-drug conjugate showed an encouraging overall response rate (ORR) in patients who were previously treated with a checkpoint inhibitor. Data presented by Rosenberg showed complete responses in four patients and partial responses in 41 patients for an ORR of 41 percent.

In the 89 patients with prior checkpoint inhibitor therapy, the ORR was 40 percent; 44 percent in the 23 patients who did not receive a checkpoint inhibitor; and 39 percent in the 33 patients with liver metastasis.

“We are encouraged by these updated data for enfortumab vedotin, which further support the rapid expansion of a comprehensive clinical trial program and the registrational study that is already underway in metastatic urothelial cancer,” Steven Benner, M.D., senior vice president and global therapeutic area head of Oncology Development at Astellas, said in the release. “We look forward to working closely with our partner, Seattle Genetics, as we continue to evaluate enfortumab vedotin for patients with metastatic urothelial cancer.”

Interim results showed a median overall survival of 13.6 months for all patients enrolled. The overall median duration of response was 5.75 months and median progression-free survival was 5.4 months.

Fifty-four percent of patients reported fatigue as a treatment-related side effect. Grade 3 or higher side effects included anemia, hyponatremia (when the sodium level in the blood is too low), urinary tract infection and hyperglycemia. Four patients died due to respiratory failure, urinary tract obstruction, diabetic ketoacidosis or multi-organ failure.

Enfortumab vedotin is being studied as a monotherapy, such as this phase 1 study, and in combination with a checkpoint inhibitor for locally advanced or metastatic urothelial cancer. In March, the Food and Drug Administration (FDA) granted enfortumab vedotin a breakthrough therapy designation.

“These ASCO data from the phase 1 study of enfortumab vedotin further support its breakthrough therapy designation from the FDA, and the rationale for our ongoing pivotal trial, EV-201,” Robert Lechleider, M.D., senior vice president of clinical development at Seattle Genetics, said in the release. “We look forward to completing enrollment of the EV-201 pivotal trial for patients with metastatic urothelial cancer who have received both a platinum-based therapy and a checkpoint inhibitor. Positive data in this patient subgroup may represent a potential expedited registration pathway.”