Seattle Genetics and its partner, Astellas, have recently announced that the patients were selected for EV-201, the key phase II clinical trial of an experimental antibody-drug conjugate (ADC) called enfortumab vedotin. The study was conducted in patients with locally advanced or metastatic urothelial carcinoma (UC) who had previously undergone checkpoint inhibitor (CPI) treatment. The efficacy and safety data from the first cohort of the study will be available in the first half of 2019 and will help enfortumab vedotin pass the regulatory application through Accelerated Approval designation of the US FDA.

In addition, the two sides also announced that the first patient in the Phase III clinical study EV-301 has received treatment. It is a global randomized study conducted in previously treated patients with locally advanced or metastatic UC, and data from this study will be used for a broader global regulatory application.

In the United States, the FDA has granted the Breakthrough Therapy to enfortumab vedotin for the treatment of patients with locally advanced or metastatic UC who has previously received CPI therapy. Apart from EV-201 and EV-301, the two sides are also conducting a phase I clinical study (EV-103), which combines enfortumab vedotin with Merck’s PD-1 immunotherapy Keytruda (pembrolizumab) for first-line treatment of patients with locally advanced or metastatic UC who is not suitable for cisplatin chemotherapy. Meanwhile, both parties are also evaluating enfortumab vedotin for other solid tumors, including ovarian cancer and non-small cell lung cancer.

Enfortumab vedotin is an experimental ADC drug linked by a monoclonal antibody targeting the nectin-4 protein and a microtubule disruptor vedotin (MMAE) via Seattle Genetics’ proprietary conjugated technology. Enfortumab vedotin targeting the Nectin-4 protein is a cell adhesion molecule discovered by Astellas that acts as an ADC target and is expressed in many solid tumors.

ADC is a new class of therapeutic drugs that is receiving increasing attention from pharmaceutical companies worldwide. ADC drugs are potent anticancer drugs targeting cancer cell conjugated by monoclonal antibodies and toxic drugs through biologically active linkers. The drug effect is greatly improved and the side effects are reduced by accurately identifying targets while leaving non-cancer cells unaffected.

antibody drug conjugates

In March of this year, Seattle Genetics announced the advancement of an innovative ADC drug, the SGN-CD48A, for clinical development. The SGN-CD48A incorporates the company’s latest ADC technology innovation, a new generation of polyethylene glycol glucoside linkers, to improve drug stability in the blood circulation system, reduce off-target absorption, and enable each CD48-targeting monoclonal antibody molecule conjugated to more disrupted microtubule cytotoxic agent MMAE. And the drug can release a larger amount of MMAE after being internalized by CD48-positive tumor cells, while MMAE can block cell division by inhibiting the polymerization of tubulin. With this novel linker, SGN-48A has demonstrated potent antitumor activity in preclinical studies.