The multi-national phase 3 clinical trial on the novel drug as a treatment option for patients with advanced bladder cancer after theyâ€™ve received standard chemotherapy and immune treatments.
A novel drug called enfortumab vedotin (EV) produced responses in 44% of patients with locally advanced or metastatic urothelial cancer who had been previously treated with chemotherapy and immune therapy using checkpoint inhibitors. The findings were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.
The multi-national phase 3 clinical trial led by researchers through the Yale Cancer Center and Smilow Cancer Hospital focused on the novel drug as a treatment option for patients with advanced bladder cancer after they’ve received standard chemotherapy and immune treatments.
“There is a high unmet need for patients with advanced and metastatic urothelial carcinoma,” lead study author Daniel P. Petrylak, MD, professor of medicine and urology at Yale Cancer Center, said at the annual meeting. “Enfortumab vedotin is the first novel therapeutic agent to demonstrate substantial clinical activity in patients who progressed after platinum chemotherapy or a PD-1 or PD-L1 inhibitor.”
The study included approximately 125 patients with 70% being male and a median age of 69 years; group 1 had received platinum chemotherapy and a PD-1 or PD-L1 and group 2 had not received either therapy. Patients received 1.25 mg/kg enfortumab vedotin intravenously on days 1, 8, and 15 of each 28-day cycle. Researchers noted that their endpoints included objective response rate, progression-free survival (PFS), median duration of response, overall survival (OS), and safety/tolerability.
Approximately 12% of the patient population in the study who were randomized to receive both standard chemotherapy plus a checkpoint inhibitor and EV had a complete response with no detectable sign of cancer. The median OS with the combination was 11.7 months, median PFS was 5.8 months, and median duration of response was 7.6 months. Also, 38% of patients whose cancer had metastasized to the liver, a site which has been resistant to both standard chemotherapy and immune therapy, responded to the treatment, according to Dr Petrylak.
Responses were observed across all subgroups, irrespective of response to prior PD-1/L1 inhibitors or presence of liver metastases. The median time to response was 1.8 months with an ongoing response rate of 44%.
The most common treatment-related adverse events of any grade were fatigue, alopecia, and decreased appetite. Twelve percent of patients discontinued treatment due to a TRAE due to peripheral neuropathy.
“We feel that both of these trials support the submission to the FDA for accelerated approval,” Dr Petrylak said. In March 2018, the FDA granted a breakthrough therapy designation to EV for patients with locally advanced or metastatic urothelial cancer that has progressed during or following checkpoint inhibitor therapy based on phase 1 trial results.
EV works as an antibody-drug conjugate, a type of therapy that combines an antibody that targets a specific protein on the surface of tumor cells with chemotherapy. According to the press release, EV uses an antibody that targets the protein known as Nectin-4, expressed in high levels on the surface of urothelial tumor cells and low levels in normal cells. This antibody is chemically linked with an agent that penetrates the tumor cell and destroys its structure.
There are 2 additional ongoing trials examining this drug therapy. The randomized phase 3 EV-301 trial is evaluating EV compared with standard-of-care post-platinum and a PD-1/L1 inhibitor and EV-103 will investigate the agent in combination with pembrolizumab and/or chemotherapy.