The US Food and Drug Administration (FDA) granted accelerated approval to enfortumab vedotin-ejfv (Padcev) made by Astellas Pharma for patients with locally advanced or metastatic urothelial cancer whose disease has progressed on platinum-based chemotherapy and immunotherapy. By targeting the cell adhesion molecule Nectin-4—highly expressed in urothelial cancers such as bladder cancers—the drug represents an antibody-drug conjugate, a strategic tool in targeted treatment of cancer.

Accelerated Approval

The FDA granted Padcev Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. The sponsor (Astellas) must conduct a confirmatory trial to verify and describe Padcev’s clinical benefit.

The FDA granted the Astellas application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a severe disease or condition. Preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Padcev received approval approximately three months before the goal date.

FDA Comment

Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence commented, “Antibody-drug conjugates are strategic tools in the targeted treatment of cancer. These conjugates combine the ability of monoclonal antibodies to target specific receptors on cancer cells and then deliver a drug to the cancer cell.” He continued, “Padcev is an antibody-drug conjugate that targets Nectin-4, a cell surface protein expressed on bladder cancer cells and a cell-killing agent, monomethyl auristatin E.”

 Clinical Trial

In a Phase 2 trial of 125 patients with locally advanced or metastatic urothelial cancer previously treated with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy, the newly approved drug led to a 12% complete response rate and a 32% partial response rate lasting a median of 7.6 months.

Recommended Dose

With a recommended dose of 1.25 mg/kg (up to a maximum dose of 125 mg), the drug is administered as an intravenous infusion over 30 minutes on Days 1,8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

Side Effects

Common side effects included fatigue, peripheral neuropathy, decreased appetite, rash, nausea, and other conditions. Blood levels should be monitored closely to avoid diabetic ketoacidosis. If new or worsening neuropathy occurs, the drug’s use should be reduced or discontinued. The FDA advises health care professionals caution patients of reproductive age to use effective contraception during treatment with Padcev and for a period of time after that. Women who are pregnant or breastfeeding should not take Padcev because it may cause harm to a developing fetus or newborn baby, or cause delivery complications. Other issues reported include dry eyes and vision changes, so review all side effects very carefully.

Next Steps

Astellas is sponsoring a Phase III, randomized confirmatory trial (EV-301). Required by the FDA as a condition for approval, the purpose of this study is to compare the overall survival (OS) of participants with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of participants treated with chemotherapy. This study will also compare progression-free survival on study therapy (PFS1), the overall response rate (ORR), and the disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of participants treated with EV to participants treated with chemotherapy. Also, this study will evaluate the duration of response (DOR) per RECIST V1.1 of EV and chemotherapy and assess the safety and tolerability of EV, as well as the quality of life (QOL) and Patient-Reported Outcomes (PRO) parameters.

Source: FDA

Pin It on Pinterest