Featured Image: Using fire as a symbol of cancer of the internal organs, including bladder, liver, and kidneys. Courtesy: © 2017. Fotolia. Used with permission.

Seattle Genetics and Astellas Pharma today confirmed dosing the first patient in EV-201, a registrational phase II clinical trial of enfortumab vedotin as a monotherapy for patients with locally advanced or metastatic urothelial cancer who have been previously treated with checkpoint inhibitor or CPI therapy.[1]

Urothelial cancer is most commonly found in the bladder. 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.

Our decision to move forward with this registrational trial is based on the results of our ongoing Phase I study… [with] enfortumab vedotin…

One potential treatment option being investigated in a number of clinical trials is enfortumab vedotin, an investigational antinody-drug conjugate or ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent called Monomethyl Auristatin E, also known as MMAE. The drug uses Seattle Genetics’ proprietary, industry-leading linker technology.

Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target by Agensys, an affiliate of Astellas, which is expressed on many solid tumors.

Advertisement #3

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.

The EV-201 trial is designed to assess the antitumor activity and safety of enfortumab vedotin to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations.

Schematic 1.0: NCT03219333 (EV-201) is a clinical trial designed to evaluate how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body. This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer. Furthermore, this study will evaluate if the Locally Advanced or Metastatic Urothelial Cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect.

“Our decision to move forward with this registrational trial is based on the results of our ongoing Phase I study, and we look forward to future clinical development milestones for enfortumab vedotin,” noted Astellas President and Chief Executive Officer Yoshihiko Hatanaka,

“Locally advanced or metastatic urothelial cancers are often aggressive and treatment-resistant. Treatment options are limited for those many patients who do not respond to chemotherapy and checkpoint inhibitors, or CPIs. In addition, there are no FDA-approved therapies for patients who progress following CPI treatment,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics.

“Initiation of this pivotal phase 2 trial of enfortumab vedotin is a significant advance toward our goal of providing a new treatment option for locally advanced or metastatic urothelial cancer,” Drachman.

Study design
The primary endpoint of the single-arm, open-label trial is confirmed objective response rate or ORR, per independent review. Secondary endpoints include assessments of overall survival, progression free-survival, safety and tolerability. The study will enroll approximately 120 patients at multiple centers globally, and enfortumab vedotin will be administered three of every four weeks for the duration of treatment.

“The initiation of the EV-201 clinical trial demonstrates our continued commitment to patients living with locally advanced or metastatic urothelial cancer,” said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas.

“Our decision to move forward with this registrational trial is based on the results of our ongoing Phase I study, and we look forward to future clinical development milestones for enfortumab vedotin.”

Seattle Genetics and Astellas Pharma also plan to initiate a combination trial of enfortumab vedotin with CPI therapy in late 2017.

Astellas and Seattle Genetics started their ADC-development collaboration in January 2007 and expanded it in November 2009. Under the collaboration, the companies are co-developing and have options to globally co-commercialize enfortumab vedotin.

Advertisement #4