Enfortumab Vedotin + Radiation for Bladder Cancer

(STAR-EV Trial)

Overseen By Amy Rowell

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Investigational agents

Disqualifiers: Prior systemic therapy, Neuropathy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

19 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for people with muscle-invasive bladder cancer. Researchers aim to determine how well enfortumab vedotin (a type of chemotherapy) works with radiation before bladder removal surgery. Three treatment approaches are being tested to identify the safest and most effective option. Individuals with bladder cancer who cannot undergo standard chemotherapy and require surgery might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot be on other investigational agents for bladder cancer during the study.

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

Research shows that enfortumab vedotin is generally well-tolerated by patients with bladder cancer, though some side effects may occur. The most common issues include nerve damage, skin problems like itching, and tiredness. A small number of patients have experienced serious side effects, such as severe skin reactions and infections.

The FDA has already approved enfortumab vedotin for treating certain types of bladder cancer, indicating a level of established safety. However, its use with radiation therapy remains under study. Participation in this trial helps researchers learn more about the effectiveness and safety of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for bladder cancer?

Unlike the standard treatments for bladder cancer, which often include chemotherapy or immunotherapy, Enfortumab Vedotin is unique because it combines an innovative antibody-drug conjugate with targeted therapy. This drug specifically delivers a powerful anti-cancer agent directly to cancer cells, potentially minimizing damage to healthy cells. Adding radiation therapy at different stages enhances its ability to attack tumors more effectively. Researchers are excited because this approach could improve precision in treatment and offer better outcomes with fewer side effects.

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

Research shows that enfortumab vedotin, a treatment under study in this trial, may hold promise for advanced bladder cancer when combined with radiation therapy. Studies have found that enfortumab vedotin significantly improves survival rates compared to standard chemotherapy for patients with advanced bladder cancer. In this trial, participants will receive various schedules of enfortumab vedotin and radiation therapy. Enfortumab vedotin has proven effective even for patients who have previously tried treatments like chemotherapy or immune therapies. These findings suggest that adding radiation to enfortumab vedotin could enhance its effectiveness, offering a potentially beneficial approach for treating muscle-invasive bladder cancer before surgery. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with muscle invasive bladder cancer who are not suitable for cisplatin chemotherapy. They must have certain blood cell counts, liver and kidney function levels, no severe neuropathy or hearing loss, and cannot be on dialysis. A good performance status (able to carry out daily activities) is required.

Inclusion Criteria

My platelet count is at least 100,000 per microliter.

My hemoglobin level is at least 9 g/dL.

I am fully active or can carry out light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive Enfortumab Vedotin and stereotactic radiotherapy as neoadjuvant treatment

9 weeks

3 cycles of Enfortumab Vedotin with concurrent or sequential radiotherapy

Surgery

Standard of care radical cystectomy and pelvic lymph node dissection with urinary diversion

1 week

Follow-up

Participants are monitored for safety and effectiveness after surgery

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin

Trial Overview The STAR-EV study tests enfortumab vedotin combined with radiotherapy before surgery in three increasing dose levels to find the safest and most effective regimen against bladder cancer that can't be treated with cisplatin.

How Is the Trial Designed?

Group I: Dose Level 2 Experimental Treatment 1 Intervention

Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 1 Day 15 of EV treatment (32.5 Gray in 5 fractions)

Group II: Dose Level 1 Experimental Treatment 1 Intervention

Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and concurrent Radiation Therapy starting on Cycle 2 Day 15 of EV treatment (32.5 Gray in 5 fractions)

Group III: Dose Level 0 Experimental Treatment 1 Intervention

Neoadjuvant therapy of Enfortumab Vedotin 1.25 mg/kg (3 cycles) and sequential Radiation Therapy starting on Cycle 3 Day 21 of EV treatment (32.5 Gray in 5 fractions)

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?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

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

Published Research Related to This Trial

In a study of 34 patients with metastatic urothelial carcinoma treated with enfortumab vedotin, 56% showed a partial response or stable disease, with a median overall survival of 16 months and progression-free survival of 9 months, indicating its efficacy in a real-world setting.

The treatment was associated with a high incidence of adverse events, with 76% of patients experiencing some level of toxicity, primarily skin-related, but the safety profile was consistent with findings from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort. Miyake, M., Nishimura, N., Oda, Y., et al.[2023]

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]

In a study of 487 bladder cancer patients treated with radical radiotherapy, the incidence of severe acute toxicity was relatively low, with 5% experiencing grade 3 or higher bladder toxicity and 3% for bowel toxicity, indicating that the treatment is generally safe.

The severity of acute toxicity was influenced by factors such as the T-stage of the cancer and the intensity of the radiation dose, with higher dose intensity leading to quicker onset of acute toxicity and a greater risk of late effects in both bladder and bowel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late toxicity in radical radiotherapy for bladder cancer. Majewski, W., Tarnawski, R.[2009]

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-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]

Recent advancements in radiation treatment planning and delivery for bladder cancer can improve treatment outcomes by minimizing damage to healthy tissue while allowing for higher radiation doses or more aggressive treatment schedules.

The review highlights the importance of patient selection and the use of techniques like image-guided radiotherapy and intensity-modulated radiotherapy to enhance treatment accuracy and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy for muscle-invasive bladder cancer: treatment planning and delivery in the 21st century. McBain, CA., Logue, JP.[2019]

In a study of 149 patients with bladder cancer, delivering a higher radiation dose to just the tumor area (partial bladder radiotherapy) did not improve local tumor control compared to whole bladder radiotherapy, with similar overall survival rates across all treatment groups.

The study found that while the increased radiation dose did not lead to higher toxicity, it also did not significantly enhance overall survival, indicating that simply increasing the dose to the tumor may not be sufficient for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy. Cowan, RA., McBain, CA., Ryder, WD., et al.[2006]

In a study of 38 patients with invasive bladder cancer, concurrent radiotherapy and panitumumab after chemotherapy resulted in a low rate of severe toxicity (16%), comparable to historical rates for cisplatin and radiotherapy.

The treatment achieved a high complete remission rate of 94%, with promising bladder preservation outcomes, suggesting that this approach could be a viable alternative for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. Fransen van de Putte, EE., Pos, F., Doodeman, B., et al.[2019]

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]

Radiotherapy remains the most effective non-surgical treatment for bladder cancer, with advancements in three-dimensional imaging improving accuracy and reliability in treatment planning.

Combining radiotherapy with chemoradiation has shown improved outcomes in one randomized-controlled trial, and hypoxia modification techniques are currently being evaluated for their potential benefits in enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies in bladder cancer. Alonzi, R., Hoskin, P.[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]

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. 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.

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

Enfortumab Vedotin and Pembrolizumab in Untreated ... Conclusions: Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with ...

4. 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.

5. 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 ...

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. 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%), ...

8. 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 ...

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- ...