Astellas and Seattle Genetics, Inc. (NASDAQ: SGEN) highlighted updated phase 1 data for enfortumab vedotin (ASG-22ME) studied as monotherapy treatment for metastatic urothelial cancer (mUC) in an oral presentation at the American Society of Clinical Oncology (ASCO) 52nd Annual Meeting in Chicago. Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a cell surface protein expressed in multiple solid tumors including mUC, ovarian cancer, and non-small cell lung cancer (NSCLC). Based on the data from the ongoing phase 1 clinical trial, the companies this year plan to initiate a registrational monotherapy phase 2 trial for locally advanced or mUC patients who have been previously treated with checkpoint inhibitor (CPI) therapy. A trial evaluating enfortumab vedotin in combination with CPIs is also planned for later this year as part of a broad clinical development program.

"Patients with metastatic urothelial cancer typically have a five-year survival rate of just five percent and are in urgent need of new treatment options. Despite recent clinical advances, up to 80 percent of patients fail to respond to checkpoint inhibitors, or CPIs, and there are no approved therapeutic options for use after CPI failure," said Daniel P. Petrylak, M.D., Ph.D., Yale Cancer Center and presenter of the phase 1 data at ASCO. "The objective response rates observed in our phase 1 analysis of enfortumab vedotin show the potential benefit of this agent for patients with metastatic urothelial cancer, particularly those who have failed CPI therapy. Enfortumab vedotin was generally well-tolerated, and the most common adverse events were nausea, itching, fatigue and diarrhea."

"We are encouraged by the data we've seen so far in the enfortumab vedotin clinical trials," said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas. "We're pleased to be moving forward the enfortumab vedotin development program in support of patients who may benefit from this new potential treatment option."

"Our updated enfortumab vedotin monotherapy phase 1 data at ASCO continue to show encouraging antitumor activity and a well-tolerated safety profile in patients with heavily pretreated metastatic urothelial cancer. We plan to initiate this year a pivotal phase 2 study in the CPI-pretreated setting with the intent of pursuing accelerated approval from the FDA," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "Enfortumab vedotin is our first late-stage clinical program for solid tumors, and these data demonstrate the potential for antibody-drug conjugates to provide therapeutic benefit across a wide array of cancers."

The following updated results from the ongoing phase 1 study evaluating enfortumab vedotin as a monotherapy for mUC were presented by Dr. Petrylak on Monday, June 5:

A Phase I Study of Enfortumab Vedotin (ASG-22CE; ASG-22ME): Updated Analysis of Patients with Metastatic Urothelial Cancer (Abstract #106, oral presentation on Monday, June 5 at 9:45 a.m. CT)
The ongoing trial is evaluating the safety and anti-tumor activity of enfortumab vedotin at escalating doses of 0.5 to 1.25 milligrams per kilogram (mg/kg) weekly for three of every four week cycles. Data were reported from 81 patients diagnosed with mUC and a median age of 67 years. Of these patients, 37 (46 percent) were previously treated with CPIs and 77 (95 percent) had undergone treatment with a platinum-based chemotherapy. Ninety-seven percent of patient screening samples showed Nectin-4 expression, the majority of which were at a high level. All response rates include confirmed and unconfirmed responses, as assessed by the investigator. The recommended phase 2 dose (RP2D) has been established at 1.25 mg/kg. Key findings include:

Of the 71 patients evaluated for response, 29 patients (41 percent) had an objective response, including three (four percent) complete responses and 26 (37 percent) partial responses. Disease control was achieved in 51 patients (72 percent), defined as the sum of patients achieving complete responses, partial responses or stable disease. The preliminary estimate of median duration of response for all patients was 24 weeks.
In 30 patients treated at the RP2D level, 16 patients (53 percent) had an objective response, including one (three percent) complete response and 15 (50 percent) partial responses. Disease control was achieved for 22 patients (73 percent).
Of the 32 patients previously treated with CPIs and evaluated for response, 14 patients (44 percent) had an objective response, including one complete response (three percent) and 13 (41 percent) partial responses. At the RP2D, eight out of 17 CPI-treated patients (47 percent) achieved a partial response, and disease control occurred in 13 patients (77 percent).
Of the 19 patients with liver metastases, nine (47 percent) had an objective response, including one (five percent) complete response and eight (42 percent) partial responses. Disease control was achieved for 13 patients (68 percent).
The most common treatment-related adverse events of any grade occurring in 10 percent or more of patients were nausea (36 percent), pruritus (31 percent), fatigue (30 percent) and diarrhea (28 percent). The most common Grade 3 or 4 adverse events occurring in five percent or more of patients, regardless of attribution, were urinary tract infections, hypophosphatemia, hyponatremia and anemia.
These results support further development of enfortumab vedotin as monotherapy and in combination with other therapies for patients with mUC. Enrollment is ongoing at the RP2D in patients with mUC who have been previously treated with CPIs.
More information about this clinical trial (NCT02091999), including enrolling centers, is available by visiting www.clinicaltrials.gov.

About Urothelial Cancer
Urothelial cancer is most commonly found in the bladder (90 percent). According to the American Cancer Society, approximately 79,000 people in the U.S. will be diagnosed with bladder cancer during 2017 and almost 17,000 will die from the disease. Outcomes are poor for patients diagnosed with metastatic disease, with a five-year survival rate of five percent.

About Enfortumab Vedotin
Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics' proprietary, industry-leading linker technology. Enfortumab vedotin is the first and only agent to target Nectin-4, a cell adhesion molecule identified as an ADC target by Agensys (an affiliate of Astellas), which is expressed on many solid tumors.

Nectin-4 is highly expressed in urothelial cancers, particularly in bladder cancer. Preclinical data demonstrate that enfortumab vedotin binds to Nectin-4 on cancer cells and releases the cell-killing agent into these target cells upon internalization.

About Astellas
Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products.