BOTHELL - Seattle Genetics, Inc. (Nasdaq: SGEN) today provided an update on the phase 1b/2 multicohort EV-103 trial (also known as KEYNOTE-869) of PADCEVTM (enfortumab vedotin-ejfv) in combination with anti-PD-1 therapy pembrolizumab for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.
Based on recent discussions with the U.S. Food and Drug Administration (FDA), data from the randomized cohort K, along with other data from the EV-103 trial evaluating PADCEV combined with pembrolizumab as first-line therapy for cisplatin-ineligible patients, could potentially support registration under accelerated approval regulations in the United States. PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.1
'We are excited that EV-103 provides PADCEV with a potential pathway for U.S. accelerated approval in first-line metastatic urothelial cancer,' said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. 'Our initial data on the combination of PADCEV and pembrolizumab in previously untreated patients who could not receive cisplatin are encouraging.'
EV-103 is a multi-cohort, open-label, multicenter phase 1b/2 trial of PADCEV alone or in combination, evaluating safety, tolerability and efficacy in muscle invasive urothelial cancer, and in locally advanced or metastatic urothelial cancer in first- or second-line settings. Cohort K from EV-103 is intended to enroll 150 patients randomized 1:1 to PADCEV monotherapy or PADCEV in combination with pembrolizumab in locally advanced or metastatic urothelial cancer patients who are ineligible for cisplatin-based chemotherapy. The primary outcome measure is objective response rate (ORR) per blinded independent central review (BICR) using RECIST 1.1 and duration of response (DoR).
In addition to EV-103, the recently initiated EV-302 phase 3 randomized clinical trial is intended to support global registrations and potentially serve as a confirmatory trial if accelerated approval is granted based on EV-103. The EV-302 trial is evaluating the combination of PADCEV and pembrolizumab with or without chemotherapy versus chemotherapy alone in patients with previously untreated locally advanced or metastatic urothelial cancer. Importantly, EV-302 includes metastatic urothelial cancer patients that are either eligible or ineligible for cisplatin-based chemotherapy. The trial is expected to enroll 1,095 patients and has dual primary endpoints of progression-free survival and overall survival. Both the EV-103 and EV-302 trials are being conducted in collaboration with Astellas and Merck.
FDA recently granted Breakthrough Therapy designation for PADCEV in combination with pembrolizumab for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting based on initial results from the EV-103 trial.
PADCEV (enfortumab vedotin-ejfv) was approved by the FDA in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.2
About Bladder and Urothelial Cancer
It is estimated that approximately 81,000 people in the U.S. will be diagnosed with bladder cancer in 2020.3 Urothelial cancer accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.4 Globally, approximately 549,000 people were diagnosed with bladder cancer in 2018, and there were approximately 200,000 deaths worldwide.5
About PADCEV
PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.6,7 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).8 PADCEV is co-developed by Astellas and Seattle Genetics.
About Seattle Genetics
Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in people's lives. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland and the European Union.
About the Astellas and Seattle Genetics Collaboration
Seattle Genetics and Astellas are co-developing PADCEV under a collaboration that was entered into in 2007 and expanded in 2009. Under the collaboration, the companies are sharing costs and profits on a 50:50 basis worldwide.
About the Seattle Genetics, Astellas and Merck Collaboration
Seattle Genetics and Astellas entered a clinical collaboration agreement with Merck to evaluate the combination of Seattle Genetics' and Astellas' PADCEV and Merck's KEYTRUDA (pembrolizumab), in patients with previously untreated metastatic urothelial cancer. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Seattle Genetics Forward-Looking Statements
Certain statements made in this press release are forward looking, such as those, among others, relating to the potential of data from the EV-103 clinical trial to support accelerated approval in the U.S. of PADCEV in combination with pembrolizumab for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting; the possibility of using data from the EV-302 clinical trial to obtain global regulatory approval or confirm accelerated approval of PADCEV in the referenced first line setting; clinical development plans relating to PADCEV; the therapeutic potential of PADCEV; and its possible safety, efficacy, and therapeutic uses, including in the first-line setting. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that ongoing and subsequent clinical trials of PADCEV may fail to produce data sufficient to support regulatory approvals; the fact that FDA has not made a final determination regarding whether the data from the EV-103 clinical trial will be sufficient to support accelerated approval in the U.S.; the risk that the COVID-19 pandemic could delay our ability to conduct the EV-103 clinical trial and delay FDA's regulatory timelines, including with respect to any potential accelerated approval; the fact that adverse events or safety signals may occur and that adverse regulatory actions or other setbacks could occur as PADCEV advances in clinical trials even after promising results in earlier clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption 'Risk Factors' included in the company's Annual Report on Form 10-K for the year ended December 31, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
Contact:
Monique Greer
Tel: (425) 527-4641
Email: mgreer@seagen.com
SEAGEN INC. 
