- Enfortumab vedotin plus pembrolizumab continues to demonstrate superior efficacy versus chemotherapy in a broad population, reinforcing the combination as standard of care in first-line treatment of la/mUC
- At nearly 30 months of follow-up in the Phase 3 EV-302 trial, the combination doubled median overall survival and progression-free survival compared to chemotherapy, with no new safety signals identified
NEW YORK, NY, USA & TOKYO, Japan I February 10, 2025 I Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) today announced additional follow-up results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) evaluating the efficacy and safety of PADCEV® (enfortumab vedotin-ejfv), a Nectin-4 directed antibody-drug conjugate, plus KEYTRUDA® (pembrolizumab), a PD-1 inhibitor, in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). The results showed a sustained overall survival (OS) and progression-free survival (PFS) benefit consistent with the findings of the primary analysis after an additional 12 months of follow-up (median follow-up of 29.1 months).1,2 These data will be presented during a rapid oral session (Abstract 664) at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) 2025 in San Francisco, CA, on February 14 at 4:10pm PT.
Thomas Powles, M.R.C.P., M.D., Professor of Genitourinary Oncology at Queen Mary University of London; Director, Barts Cancer Center, London; EV-302 Primary Investigator
“These latest findings from the EV-302 trial reaffirm the primary results, which demonstrated survival improvements for patients treated with enfortumab vedotin and pembrolizumab that were previously unprecedented in locally advanced or metastatic urothelial cancer. These data show that the potential survival benefit has become even more robust with extended follow up and further solidify the combination as standard of care.”
Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% confidence interval [CI], 0.43-0.61). The median OS was 33.8 months for the combination versus 15.9 months for chemotherapy. The OS benefit was observed in all prespecified subgroups, including cisplatin eligible and ineligible subgroups. Enfortumab vedotin plus pembrolizumab also reduced the risk of disease progression or death by 52% versus chemotherapy (HR = 0.48, 95% CI, 0.41-0.57). The median PFS was 12.5 months for the combination versus 6.3 months for chemotherapy. The safety profile was consistent with previous findings and no new safety concerns were identified.1
Please see Important Safety Information at the end of this press release, including BOXED WARNING for enfortumab vedotin.
In addition to longer follow-up data, an exploratory analysis evaluating treatment outcomes and safety profile in patients with confirmed complete response (cCR) will also be presented. Among patients evaluable for response, confirmed objective response rate (cORR) was 67.5% for enfortumab vedotin plus pembrolizumab compared to 44.2% for chemotherapy. Median duration of response (DOR) was 23.3 months (95% CI, 17.8-not estimable [NE]) for the combination and 7.0 months (95% CI, 6.2-9.0) for chemotherapy. A cCR was achieved in 30.4% of patients treated with enfortumab vedotin plus pembrolizumab and 14.5% of patients treated with chemotherapy. Median duration of cCR was not reached for the combination and 15.2 months (95% CI, 10.3-NE) for chemotherapy. In patients with cCR, grade ≥3 treatment-related adverse events occurred in 61.7% of patients in the enfortumab vedotin plus pembrolizumab arm compared to 71.9% in the chemotherapy arm. There were no treatment-related deaths in the cCR subgroup.1
Roger Dansey, M.D., Chief Oncology Officer, Pfizer
“Patients with bladder cancer can face a poor prognosis, particularly in the advanced stages, and until recently had few available treatment options. The updated EV-302 results show sustained long-term efficacy in a broad population that includes both cisplatin eligible and ineligible patients and reinforce this combination’s ability to reshape the urothelial cancer treatment landscape.”
Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
“The combination of enfortumab vedotin and pembrolizumab was the first approval to offer an alternative to platinum-containing chemotherapy, which had been the standard of care for first-line locally advanced or metastatic urothelial cancer for decades. We are delighted that the additional follow-up results of the EV-302 trial show a durable benefit. These data represent yet another milestone in our long-standing commitment to helping patients around the world live longer and healthier lives.”
Enfortumab vedotin plus pembrolizumab is approved for the treatment of adult patients with la/mUC in the United States, the European Union, Japan and a number of other countries around the world. Enfortumab vedotin is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-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.3
+++
About EV-302
The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.4
The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Primary results from the EV-302 study were presented at the European Society for Medical Oncology (ESMO) Congress in October 2023.
About PADCEV® (enfortumab vedotin-ejfv)
PADCEV ® (enfortumab vedotin-ejfv) 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.5 Nonclinical data suggest the anticancer activity of enfortumab vedotin 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).3
PADCEV ® (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information
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.
Indication
PADCEV®, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC).
PADCEV, as a single agent, is indicated for the treatment of adult patients with locally advanced or 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.
For more information, please see the U.S. full Prescribing Information including BOXED WARNING for PADCEV here.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Astellas
Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women’s health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at www.astellas.com.
About the Pfizer, Astellas and Merck Collaboration
Seagen and Astellas entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen’s and Astellas’ PADCEV® (enfortumab vedotin-ejfv) and Merck’s KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. Pfizer Inc. successfully completed its acquisition of Seagen on December 14, 2023. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada).
References
1 Powels T, et al. EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). J Clin Oncol 43, 2025 (suppl 5; abstr 664)
2 Powels T, Valderrama BP, Gupta S, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med 2024;390:875-888.
3 PADCEV [package insert]. Northbrook, IL: Astellas Pharma US, Inc.
4 National Cancer Institute. Enfortumab Vedotin and Pembrolizumab vs Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302). ClinicalTrials.gov identifier: NCT04223856. Published January 6, 2020. Updated September 27, 2024. Accessed January 6, 2025. https://clinicaltrials.gov/study/NCT04223856?tab=results#results-overview.
5 Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 2016;76(10):3003-13.
SOURCE: Astellas Pharma
Post Views: 164
- Enfortumab vedotin plus pembrolizumab continues to demonstrate superior efficacy versus chemotherapy in a broad population, reinforcing the combination as standard of care in first-line treatment of la/mUC
- At nearly 30 months of follow-up in the Phase 3 EV-302 trial, the combination doubled median overall survival and progression-free survival compared to chemotherapy, with no new safety signals identified
NEW YORK, NY, USA & TOKYO, Japan I February 10, 2025 I Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) today announced additional follow-up results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) evaluating the efficacy and safety of PADCEV® (enfortumab vedotin-ejfv), a Nectin-4 directed antibody-drug conjugate, plus KEYTRUDA® (pembrolizumab), a PD-1 inhibitor, in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). The results showed a sustained overall survival (OS) and progression-free survival (PFS) benefit consistent with the findings of the primary analysis after an additional 12 months of follow-up (median follow-up of 29.1 months).1,2 These data will be presented during a rapid oral session (Abstract 664) at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) 2025 in San Francisco, CA, on February 14 at 4:10pm PT.
Thomas Powles, M.R.C.P., M.D., Professor of Genitourinary Oncology at Queen Mary University of London; Director, Barts Cancer Center, London; EV-302 Primary Investigator
“These latest findings from the EV-302 trial reaffirm the primary results, which demonstrated survival improvements for patients treated with enfortumab vedotin and pembrolizumab that were previously unprecedented in locally advanced or metastatic urothelial cancer. These data show that the potential survival benefit has become even more robust with extended follow up and further solidify the combination as standard of care.”
Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% confidence interval [CI], 0.43-0.61). The median OS was 33.8 months for the combination versus 15.9 months for chemotherapy. The OS benefit was observed in all prespecified subgroups, including cisplatin eligible and ineligible subgroups. Enfortumab vedotin plus pembrolizumab also reduced the risk of disease progression or death by 52% versus chemotherapy (HR = 0.48, 95% CI, 0.41-0.57). The median PFS was 12.5 months for the combination versus 6.3 months for chemotherapy. The safety profile was consistent with previous findings and no new safety concerns were identified.1
Please see Important Safety Information at the end of this press release, including BOXED WARNING for enfortumab vedotin.
In addition to longer follow-up data, an exploratory analysis evaluating treatment outcomes and safety profile in patients with confirmed complete response (cCR) will also be presented. Among patients evaluable for response, confirmed objective response rate (cORR) was 67.5% for enfortumab vedotin plus pembrolizumab compared to 44.2% for chemotherapy. Median duration of response (DOR) was 23.3 months (95% CI, 17.8-not estimable [NE]) for the combination and 7.0 months (95% CI, 6.2-9.0) for chemotherapy. A cCR was achieved in 30.4% of patients treated with enfortumab vedotin plus pembrolizumab and 14.5% of patients treated with chemotherapy. Median duration of cCR was not reached for the combination and 15.2 months (95% CI, 10.3-NE) for chemotherapy. In patients with cCR, grade ≥3 treatment-related adverse events occurred in 61.7% of patients in the enfortumab vedotin plus pembrolizumab arm compared to 71.9% in the chemotherapy arm. There were no treatment-related deaths in the cCR subgroup.1
Roger Dansey, M.D., Chief Oncology Officer, Pfizer
“Patients with bladder cancer can face a poor prognosis, particularly in the advanced stages, and until recently had few available treatment options. The updated EV-302 results show sustained long-term efficacy in a broad population that includes both cisplatin eligible and ineligible patients and reinforce this combination’s ability to reshape the urothelial cancer treatment landscape.”
Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
“The combination of enfortumab vedotin and pembrolizumab was the first approval to offer an alternative to platinum-containing chemotherapy, which had been the standard of care for first-line locally advanced or metastatic urothelial cancer for decades. We are delighted that the additional follow-up results of the EV-302 trial show a durable benefit. These data represent yet another milestone in our long-standing commitment to helping patients around the world live longer and healthier lives.”
Enfortumab vedotin plus pembrolizumab is approved for the treatment of adult patients with la/mUC in the United States, the European Union, Japan and a number of other countries around the world. Enfortumab vedotin is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-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.3
+++
About EV-302
The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.4
The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Primary results from the EV-302 study were presented at the European Society for Medical Oncology (ESMO) Congress in October 2023.
About PADCEV® (enfortumab vedotin-ejfv)
PADCEV ® (enfortumab vedotin-ejfv) 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.5 Nonclinical data suggest the anticancer activity of enfortumab vedotin 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).3
PADCEV ® (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information
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.
Indication
PADCEV®, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC).
PADCEV, as a single agent, is indicated for the treatment of adult patients with locally advanced or 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.
For more information, please see the U.S. full Prescribing Information including BOXED WARNING for PADCEV here.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Astellas
Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women’s health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at www.astellas.com.
About the Pfizer, Astellas and Merck Collaboration
Seagen and Astellas entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen’s and Astellas’ PADCEV® (enfortumab vedotin-ejfv) and Merck’s KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. Pfizer Inc. successfully completed its acquisition of Seagen on December 14, 2023. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada).
References
1 Powels T, et al. EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). J Clin Oncol 43, 2025 (suppl 5; abstr 664)
2 Powels T, Valderrama BP, Gupta S, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med 2024;390:875-888.
3 PADCEV [package insert]. Northbrook, IL: Astellas Pharma US, Inc.
4 National Cancer Institute. Enfortumab Vedotin and Pembrolizumab vs Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302). ClinicalTrials.gov identifier: NCT04223856. Published January 6, 2020. Updated September 27, 2024. Accessed January 6, 2025. https://clinicaltrials.gov/study/NCT04223856?tab=results#results-overview.
5 Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 2016;76(10):3003-13.
SOURCE: Astellas Pharma
Post Views: 164
