TOKYO and BOTHELL, Wash. - Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., 'Astellas') and Seagen Inc. (Nasdaq:SGEN) announced that patient enrollment was completed in Cohort K of the phase 1b/2 EV-103 clinical trial (also known as KEYNOTE-869). The cohort is evaluating PADCEV (enfortumab vedotin-ejfv) in combination with Merck's anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. Merck is known as MSD outside the United States and Canada.
'Completing enrollment in this study is an important step in investigating the potential for the combination of PADCEV and KEYTRUDA to treat metastatic urothelial cancer,' said Roger Dansey, M.D., Chief Medical Officer, Seagen. 'If results of this study are compelling, we may have the opportunity to submit them to the FDA as part of an application for accelerated approval.'
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 bladder cancer and in locally advanced or metastatic urothelial cancer in first- or second-line settings. Key outcome measures of EV-103 Cohort K are objective response rate (ORR) per blinded independent central review (BICR) using RECIST 1.1 and duration of response (DoR). The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation in February 2020 for PADCEV in combination with KEYTRUDA for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. The designation is based on results from the dose-escalation cohort and expansion cohort A of the EV-103 trial.
'The FDA's Breakthrough Therapy designation is based on preliminary data on the combination of PADCEV and KEYTRUDA,' said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Head of Development Therapeutic Areas, Astellas. 'Both Cohort K of EV-103 and our ongoing, broader phase 3 EV-302 study are evaluating this platinum-free combination in patients with previously untreated advanced urothelial cancers.' EV-302 is also known as KEYNOTE-A39.
About Bladder and Urothelial Cancer
It is estimated that approximately 83,730 people in the U.S. will be diagnosed with bladder cancer in 2021.1 Urothelial cancer accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.2 Globally, approximately 573,000 new cases of bladder cancer and 212,000 deaths are reported annually.3
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.4 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).5
BOXED WARNING: SERIOUS SKIN REACTIONS
PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
Closely monitor patients for skin reactions.
Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.
PADCEV is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who: have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+ healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.
Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.
About the Astellas, Seagen and Merck Collaboration
Astellas and Seagen entered a clinical collaboration agreement with Merck to evaluate the combination of Astellas' and Seagen's PADCEV (enfortumab vedotin-ejfv) 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.
Astellas Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development), which is included in this press release, is not intended to constitute an advertisement or medical advice.
Seagen Forward Looking Statements
Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of PADCEV, its possible efficacy, safety and therapeutic uses, the referenced clinical trial and the potential for data from such trial to support an application for accelerated approval in the U.S. 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, without limitation, the failure of PADCEV to show sufficient activity in the clinical setting referenced above; adverse events and safety signals; adverse regulatory actions; delays or setbacks in the conduct of or obtaining data from clinical trials, the submission of regulatory applications and the regulatory review process for a variety of reasons, including the inherent difficulty and uncertainty of pharmaceutical product development; possible required modifications to clinical trials; the inability to provide information and institute safety mitigation measures as may be required by the FDA or other regulatory authorities from time to time; failure to properly conduct or manage clinical trials; and failure of clinical results to support continued development or regulatory approvals. More information about the risks and uncertainties faced by Seagen is contained under the caption 'Risk Factors' included in the company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 filed with the Securities and Exchange Commission. Seagen 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.
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