Enfortumab Vedotin + Pembrolizumab for Advanced Bladder Cancer

Recruiting at 3 trial locations

Overseen By Jacqueline Brown, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Investigational agents, High-dose steroids

Disqualifiers: Neuroendocrine histology, Uncontrolled diabetes, Active CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two drugs, enfortumab vedotin and pembrolizumab, in treating advanced bladder cancer that has spread. Enfortumab vedotin (Padcev) targets and kills cancer cells, while pembrolizumab (KEYTRUDA) helps the immune system attack the cancer. The trial aims to determine if these drugs together can more effectively kill cancer cells. It seeks participants with bladder cancer that has spread to nearby tissues or other parts of the body and is a less common type. Those diagnosed with this kind of bladder cancer, especially if it impacts daily life, may consider participating. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving systemic antimicrobial treatment for an active infection or high dose steroids, or if you have had chemotherapy or radiotherapy within 4 weeks prior to entering the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of enfortumab vedotin and pembrolizumab is generally well-tolerated by patients with advanced bladder cancer. Studies have found that this combination can lower the risk of certain health issues and improve survival rates for people with this type of cancer.

Enfortumab vedotin attaches to a protein on cancer cells and delivers a drug that kills them. Pembrolizumab helps the immune system attack cancer cells. Together, they offer an alternative to traditional chemotherapy.

While these treatments have shown promise, they can still cause side effects. Patients should discuss any concerns with healthcare providers to understand how these treatments might affect their health. Overall, evidence suggests these treatments are safe for many patients, but individual health conditions can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Enfortumab Vedotin and Pembrolizumab for advanced bladder cancer because this duo offers a unique approach to treatment. While traditional therapies might focus on chemotherapy or surgery, Enfortumab Vedotin is a novel antibody-drug conjugate that targets cancer cells specifically, minimizing damage to healthy cells. Additionally, Pembrolizumab is an immunotherapy that helps unleash the body’s immune system against cancer, which is different from conventional treatments. This combination has the potential not only to improve effectiveness but also to reduce side effects compared to standard options.

What evidence suggests that enfortumab vedotin and pembrolizumab might be effective for advanced bladder cancer?

Research shows that combining enfortumab vedotin and pembrolizumab may help treat advanced bladder cancer. Studies have found that this combination improves survival rates and shrinks tumors more effectively than traditional chemotherapy. Enfortumab vedotin attaches to a protein called nectin-4 on cancer cells, aiding in their destruction. Pembrolizumab enhances the immune system's ability to fight cancer by blocking a pathway that allows cancer to hide. The FDA has approved this combination for certain advanced bladder cancers, demonstrating its effectiveness. This trial will evaluate the combination of enfortumab vedotin and pembrolizumab, suggesting potential benefits for patients with advanced or metastatic bladder cancer with different cell types. ^{5 6 7 8 9}

Who Is on the Research Team?

Jacqueline Brown, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

Adults with advanced or metastatic bladder cancer of variant histology, who are fit (ECOG <=1), have not had recent treatments that could interfere, and can provide tumor samples. Women must not be pregnant and all participants must agree to use contraception. Exclusions include certain other cancers, uncontrolled illnesses, prior EV or PD-1/PD-L1 inhibitor treatment, active infections like hepatitis B/C, autoimmune diseases requiring systemic treatment within 2 years.

Inclusion Criteria

The doctor believes you will live for at least 12 more weeks.

My bladder cancer is of a specific type, not the usual kind.

I finished all my cancer treatments at least 4 weeks ago.

Exclusion Criteria

I have not had serious heart problems like heart failure or unstable angina in the last 6 months.

I have moderate to severe numbness, tingling, or muscle weakness.

I have diabetes with an HbA1c level of 7% or higher and symptoms like frequent urination or thirst.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin and pembrolizumab intravenously. They also undergo CT scan or MRI, and collection of blood throughout the trial.

Up to 2 years

Regular visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Pembrolizumab

Trial Overview The trial is testing the combination of Enfortumab Vedotin (EV) and Pembrolizumab in treating less common types of bladder cancer that has spread. EV targets nectin-4 on cancer cells to deliver a drug that kills them; Pembrolizumab helps the immune system fight cancer.

How Is the Trial Designed?

Group I: Treatment (enfortumab vedotin, pembrolizumab) Experimental Treatment 6 Interventions

Patients receive enfortumab vedotin IV and pembrolizumab IV on study. Patients also undergo CT scan or MRI, and collection of blood throughout the trial.

Enfortumab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Padcev for:

• Locally advanced or metastatic urothelial cancer

Approved in European Union as Padcev for:

• Locally advanced or metastatic urothelial cancer

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Enfortumab vedotin (Padcev) is the first FDA-approved treatment specifically for adults with locally advanced or metastatic urothelial cancer who have already undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

This approval marks a significant advancement in cancer therapy, providing a new option for patients who have limited treatment choices after previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. Kahl, KL.[2023]

The combination of enfortumab vedotin (EV) and pembrolizumab (Pembro) demonstrated a high confirmed objective response rate (cORR) of 64.5% in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, indicating its efficacy as a first-line treatment option.

Patients receiving the combination therapy also experienced durable responses, with 65.4% maintaining their response at 12 months, while the safety profile showed manageable adverse events, with no new safety signals identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. O'Donnell, PH., Milowsky, MI., Petrylak, DP., et al.[2023]

Enfortumab vedotin-ejfv (EV) is an effective treatment for locally advanced or metastatic urothelial carcinoma (UC), showing a 44% overall response rate and a median overall survival of 11.7 months in heavily pretreated patients.

While EV demonstrates significant antitumor activity, it also presents unique toxicity concerns that require careful monitoring, highlighting the need for further studies to optimize its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. Halford, Z., Anderson, MK., Clark, MD.[2021]

In a study of 45 patients with locally advanced or metastatic urothelial cancer, the combination of enfortumab vedotin and pembrolizumab resulted in tumor shrinkage in 73% of patients within 2 months, with effects lasting over 2 years.

While 16% of patients experienced serious side effects, most were manageable, although 24% had to stop treatment due to these side effects, indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. Hoimes, CJ., Flaig, TW., Milowsky, MI., et al.[2023]

Enfortumab vedotin (PADCEV) received accelerated FDA approval for treating locally advanced or metastatic urothelial cancer in patients who have already undergone specific prior therapies, based on substantial evidence from a study involving 125 patients.

The treatment showed a confirmed objective response rate of 44%, with a median response duration of 7.6 months, although 73% of patients experienced grade 3-4 adverse reactions, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. Chang, E., Weinstock, C., Zhang, L., et al.[2022]

In the EV-201 trial involving 125 patients with advanced urothelial carcinoma, enfortumab vedotin (EV) demonstrated a stable health-related quality of life (HRQoL) throughout treatment, with no worsening of global health status or physical functioning.

Patients who responded to EV therapy reported lower pain and fatigue levels, particularly those with bone metastases, suggesting potential improvements in symptoms alongside the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. McGregor, B., O'Donnell, PH., Balar, A., et al.[2023]

Enfortumab vedotin (EV) and platinum rechallenge both demonstrated comparable oncological outcomes in patients with advanced urothelial carcinoma after prior treatments, with progression-free survival (PFS) and overall survival (OS) rates being similar between the two groups.

In a study of 64 patients, both treatments showed effective results, suggesting that EV can be a viable alternative to platinum rechallenge for patients who have already undergone platinum-based chemotherapy and pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study. Taguchi, S., Kawai, T., Ambe, Y., et al.[2023]

Citations

1. merck.com merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-significantly-improved-event-free-and-overall-survival-and-pathologic-complete-response-rate-for-certain-patients-with-muscle/

KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab ... KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab vedotin-ejfv) Significantly Improved Event-Free and Overall Survival and Pathologic Complete ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06764095

NCT06764095 | Enfortumab Vedotin and Pembrolizumab ... This phase IV trial tests the impact of standard of care enfortumab vedotin and pembrolizumab followed by removal of all or part of the bladder ...

3. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-bladder-cancer/164052-esmo-2025-ev-103-cohort-k-efficacy-and-safety-of-enfortumab-vedotin-with-or-without-pembrolizumab-in-cisplatin-ineligible-patients-with-previously-untreated-locally-advanced-or-metastatic-urothelial-cancer-with-a-median-follow-up-of-3-5-years.html

ESMO 2025: EV-103 Cohort K: Efficacy and Safety ... FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38446675/

Enfortumab Vedotin and Pembrolizumab in Untreated ... Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-enfortumab-vedotin-ejfv-pembrolizumab-locally-advanced-or-metastatic-urothelial-cancer

FDA approves enfortumab vedotin-ejfv with ... FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer ... The major efficacy outcome ...

6. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-and-astellas-padcevr-enfortumab-vedotin-ejfv-plus-0

Pfizer and Astellas' PADCEV® (enfortumab vedotin-ejfv) ... The combination of enfortumab vedotin and pembrolizumab was the first approval to offer an alternative to platinum-containing chemotherapy.

7. merck.com merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-reduced-risk-of-event-free-survival-events-by-60-and-risk-of-death-by-50-for-certain-patients-with-muscle-invasive-bladder-ca/

KEYTRUDA® (pembrolizumab) Plus Padcev ... - Merck.com KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Event-Free Survival Events by 60% and Risk of Death by 50% for Certain Patients ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761137s018.pdf

Padcev - accessdata.fda.gov Nonclinical data suggest that the anticancer activity of enfortumab vedotin-ejfv is due to the binding of the ADC to Nectin-4-expressing cells, followed by ...

9. padcev.com padcev.com/trial-results

Clinical Study Results | PADCEV® (enfortumab vedotin-ejfv) See clinical study data for PADCEV® in adults with advanced bladder cancer or cancers of the urinary tract. See full PI, including Serious Side Effects.