Enfortumab Vedotin vs Chemotherapy for Bladder Cancer

Not currently recruiting at 188 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Antimicrobials, Steroids, Antivirals, others

Disqualifiers: Neuropathy, CNS metastases, Diabetes, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 21

Duration: 4.99 months for enfortumab vedotin, 3.45 months for chemotherapy

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial aims to determine if enfortumab vedotin, a new treatment, extends the lives of people with advanced bladder cancer compared to standard chemotherapy. Researchers will also evaluate how effectively each treatment prevents cancer progression and assess their safety and tolerability. Participants should have bladder cancer that has spread or cannot be surgically removed and should have previously tried treatments like checkpoint inhibitors and platinum-based chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are currently receiving systemic antimicrobial treatment for an infection, you may not be eligible to participate. It's best to discuss your specific medications with the study team.

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

Research shows that enfortumab vedotin (EV) is generally well-tolerated by people with bladder cancer. Earlier studies identified common side effects, including fatigue, skin rash, and nerve damage, which can usually be managed. However, about 5% of patients experienced more serious reactions, such as infections like sepsis and severe skin problems.

Enfortumab vedotin is already FDA-approved for treating bladder cancer in certain adults, indicating that its safety is well-understood. Prospective trial participants may find this information reassuring regarding its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about enfortumab vedotin for bladder cancer because it offers a novel approach compared to standard chemotherapies like docetaxel, vinflunine, and paclitaxel. Enfortumab vedotin is an antibody-drug conjugate that targets a specific protein, Nectin-4, found on the surface of bladder cancer cells. This targeted approach allows the drug to deliver its cancer-killing agent directly to the cancer cells, potentially improving effectiveness and reducing damage to healthy cells. Unlike traditional chemotherapy, which can affect both cancerous and healthy cells, enfortumab vedotin's precision in targeting could offer better outcomes and fewer side effects for patients.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that enfortumab vedotin, which participants in this trial may receive in Arm A, effectively treats advanced bladder cancer. In previous studies, patients taking enfortumab vedotin lived longer than those receiving standard chemotherapy. Specifically, 4.9% of patients experienced complete cancer remission, and 35.8% saw tumor reduction. Participants in Arm B will receive standard chemotherapy, including options like docetaxel, vinflunine, or paclitaxel. When combined with another drug, enfortumab vedotin reduced the risk of death by 49% compared to chemotherapy alone. These findings indicate that enfortumab vedotin can significantly help manage bladder cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

Adults with advanced or metastatic urothelial cancer who have previously been treated with a checkpoint inhibitor and a platinum-containing regimen. They must not be candidates for curative surgery, have acceptable organ function, agree to contraception if of childbearing potential, and cannot be breastfeeding or pregnant. Exclusions include certain preexisting conditions like neuropathy Grade ≥2, recent other cancers, active infections requiring systemic treatment, specific viral infections (HIV/Hepatitis B/C), recent cardiovascular events, untreated brain metastases among others.

Inclusion Criteria

I've had platinum-based treatment for my cancer and it progressed within a year.

I am fully active or restricted in physically strenuous activity but can do light work.

Female subject must either: Be of nonchildbearing potential: Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy). Or, if of childbearing potential: Agree not to try to become pregnant during the study and for at least 6 months after the final study drug administration, and have a negative urine or serum pregnancy test within 7 days prior to Day 1 (Females with false positive results and documented verification of negative pregnancy status are eligible for participation), and if heterosexually active, agree to consistently use a condom plus 1 form of highly effective birth control per locally accepted standards starting at screening and throughout the study period and for at least 6 months after the final study drug administration. Female subject must agree not to breastfeed or donate ova starting at screening and throughout the study period, and for at least 6 months after the final study drug administration. A sexually active male subject with female partner(s) who is of childbearing potential is eligible if: Agrees to use a male condom starting at screening and continue throughout the study treatment and for at least 6 months after final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below the subjects female partner(s) is utilizing 1 form of highly effective birth control per locally accepted standards starting at screening and continue throughout study treatment and for at least 6 months after the male subject receives final study drug administration. Male subject must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final study drug administration. Male subject with a pregnant or breastfeeding partner(s) must agree to abstinence or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for at least 6 months after the final study drug administration. Subject agrees not to participate in another interventional study while on treatment in present study

Exclusion Criteria

I am allergic to certain cancer drugs like docetaxel, paclitaxel, or vinflunine.

My diabetes has been under control for the last 3 months.

I have a known history of HIV infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either enfortumab vedotin or chemotherapy until disease progression or other discontinuation criteria are met

4.99 months for enfortumab vedotin, 3.45 months for chemotherapy

Every 21-28 days depending on treatment arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

11.10 months

Cross-over Extension

Eligible participants from the chemotherapy arm may receive enfortumab vedotin until discontinuation criteria are met

Until discontinuation criteria are met

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Enfortumab Vedotin
• Paclitaxel
• Vinflunine

Trial Overview

The trial is testing the effectiveness of Enfortumab Vedotin compared to standard chemotherapy drugs (Docetaxel, Vinflunine, Paclitaxel) in improving overall survival rates for patients with urothelial cancer. It also examines progression-free survival rates, response rates to treatment according to RECIST V1.1 criteria and evaluates safety/tolerability along with quality of life outcomes.

How Is the Trial Designed?

Group I: Cross-over Extension (COE) Experimental Treatment 1 Intervention

Eligible participants from chemotherapy arm who met the criteria for COE will receive 1.25 mg/kg of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle until discontinuation criteria is met.

Group II: Arm A: Enfortumab Vedotin 1.25 mg/kg Experimental Treatment 1 Intervention

Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Group III: Arm B: Chemotherapy Active Control 3 Interventions

Participants received either 75 milligrams per square meter (mg/m\^2) docetaxel by IV infusion over approximately 1 hour or 320 mg/m\^2 vinflunine by IV infusion over approximately 20 minutes or 175 mg/m\^2 paclitaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

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

Published Research Related to This Trial

Enfortumab vedotin, a treatment for advanced bladder cancer, can cause severe skin reactions, with a case report highlighting a patient who developed toxic epidermal necrolysis shortly after starting the drug.

The case emphasizes the need for careful monitoring of skin reactions and suggests that if such reactions occur, treatment may need to be reduced or stopped to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. Mimura, Y., Kobayashi, A., Utazu, H., et al.[2023]

Cisplatin-based combination chemotherapy has shown greater efficacy in treating advanced transitional-cell carcinoma of the bladder compared to older regimens based on Adriamycin or methotrexate, with significant patient responses reported in trials.

While regimens like CMV (cisplatin, methotrexate, and vinblastine) and M-VAC (methotrexate, vinblastine, Adriamycin, and cisplatin) demonstrate improved response rates and survival, they also come with significant toxicity, prompting ongoing phase III studies to further evaluate their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced transitional-cell carcinoma of the bladder. Miller, RS., Torti, FM.[2019]

Enfortumab vedotin showed a 44% overall response rate in a phase II trial involving 125 patients with locally advanced or metastatic urothelial carcinoma who had previously undergone platinum-based chemotherapy and PD-1 or PD-L1 checkpoint inhibitor treatment.

While nearly all patients experienced treatment-related adverse events, most of these side effects were mild to moderate, indicating a manageable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Checks Urothelial Cancer. [2020]

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]

Intravesical docetaxel (DTX) formulations, particularly those loaded in hyperbranched polyglycerols (HPGs), were well tolerated in a mouse model of bladder cancer, showing no significant local or systemic toxicities.

The HPG-loaded DTX formulation (0.5 mg/mL) was significantly more effective in reducing tumor growth compared to the commercial formulation (Taxotere), indicating a potential for improved efficacy in bladder cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo evaluation of intravesical docetaxel loaded hydrophobically derivatized hyperbranched polyglycerols in an orthotopic model of bladder cancer. Mugabe, C., Matsui, Y., So, AI., et al.[2018]

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]

Enfortumab vedotin (EV) has demonstrated promising efficacy and good tolerability in phase I/II trials for patients with metastatic urothelial carcinoma, particularly those who have been heavily pretreated or have liver metastases.

EV appears to be more effective than traditional third-line chemotherapies like vinflunine, paclitaxel, or docetaxel, indicating its potential as a valuable alternative in the treatment landscape for mUC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin - next game-changer in urothelial cancer. Maas, M., Stühler, V., Walz, S., et al.[2022]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2035807

Enfortumab Vedotin in Previously Treated Advanced ...

Enfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma.

2.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK605113/

Clinical Review - Enfortumab Vedotin (Padcev) - NCBI - NIH

Totals of 4.9% and 35.8% of patients achieved a confirmed complete response (CR) and partial response (PR), respectively, in the enfortumab vedotin arm compared ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S155876732400257X

Real-world Effectiveness of Single-Agent Enfortumab ...

EV demonstrates efficacy in patients with mUC regardless of prior receipt of platinum-based chemotherapy and PD-1/L1 inhibitors or treatment line.

4.

urotoday.com

urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-press-releases/158093-pfizer-and-astellas-padcev-enfortumab-vedotin-ejfv-plus-keytruda-pembrolizumab-shows-long-term-efficacy-in-first-line-treatment-of-locally-advanced-or-metastatic-urothelial-cancer-la-muc.html

Pfizer and Astellas' PADCEV® (enfortumab vedotin-ejfv) ...

Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11416998/

Cost-effectiveness of first-line enfortumab vedotin in addition ...

The combination therapy also reduced the risk of progression or death by 55% and nearly doubled median PFS, with an HR of 0.45 (median PFS: 12.5 ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2019/761137s000lbl.pdf

PADCEV (enfortumab vedotin-ejfv) - accessdata.fda.gov

PADCEV is a prescription medicine used to treat adults with bladder cancer and cancers of the urinary tract (renal pelvis, ureter or urethra) that has ...

7.

urotoday.com

urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-bladder-cancer/149388-asco-gu-2024-safety-and-efficacy-of-enfortumab-vedotin-in-patients-with-metastatic-locally-advanced-urothelial-cancer-real-world-evidence-from-a-european-database.html

ASCO GU 2024: Safety and Efficacy of Enfortumab Vedotin ...

The most common and relevant adverse events with EV are neurotoxicity, dermatologic toxicity/pruritis, and fatigue. Adverse events of special interest include ...

8.

padcevhcp.com

padcevhcp.com/

Official HCP Site for PADCEV® (enfortumab vedotin-ejfv)

Fatal adverse reactions occurred in 5% of patients treated with PADCEV in combination with pembrolizumab, including sepsis (1.6%), bullous dermatitis (0.8%), ...

9.

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 ...

10.

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) ...

Enfortumab vedotin plus pembrolizumab also reduced the risk of disease progression or death by 52% versus chemotherapy (HR = 0.48, 95% CI, 0.41- ...