Enfortumab Vedotin + Radiation for Bladder Cancer

Overseen By Comron Hassanzadeh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Scleroderma, Lupus, Ulcerative colitis, others

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: 5

Duration: 4-5 weeks

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of enfortumab vedotin, a cancer-fighting drug, and radiation therapy can better control bladder cancer. Researchers aim to determine the effectiveness of this combination in treating the disease. Suitable candidates have been diagnosed with specific types of bladder cancer and are eligible for local therapy, such as radiation. Participants will receive the drug intravenously and undergo radiation sessions over several weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants an opportunity to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on high doses of steroids or other immunosuppressive medications, you may not be eligible to participate.

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

Research has shown that enfortumab vedotin has been tested in people with advanced bladder cancer. These studies found it more effective in controlling the disease than traditional chemotherapy. However, safety remains a key concern. Some patients experienced side effects, which is common with cancer treatments, including tiredness, skin rash, and changes in blood sugar levels.

The current trial is in its early stages, so researchers are carefully monitoring the combination of enfortumab vedotin with radiation for safety. This phase helps determine how well patients handle this new treatment combination. Since enfortumab vedotin has been used before in advanced bladder cancer, there is some evidence of its safety, but using it with radiation therapy is new. This trial will help determine if this combination is safe and how patients react to it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Enfortumab Vedotin for bladder cancer because it offers a novel approach compared to standard treatments like chemotherapy or immunotherapy. Unlike traditional treatments, Enfortumab Vedotin is an antibody-drug conjugate, which means it directly targets cancer cells with a potent anti-cancer agent while sparing healthy cells. This targeted mechanism could potentially lead to fewer side effects and more effective cancer cell eradication. Additionally, when combined with radiation therapy, Enfortumab Vedotin might enhance the cancer-killing effects, offering a promising new option for patients.

What evidence suggests that the combination of enfortumab vedotin and radiation therapy could be effective for bladder cancer?

In this trial, participants will receive a combination of enfortumab vedotin and radiation therapy to evaluate its effectiveness in treating bladder cancer. Research has shown that enfortumab vedotin alone can significantly improve survival rates in patients with advanced bladder cancer compared to standard chemotherapy. It has proven effective for patients who have already tried other treatments, such as platinum-based chemotherapy and PD-1/L1 inhibitors. The trial aims to determine if combining it with radiation therapy can better control the disease, potentially leading to improved outcomes for people with bladder cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Comron Hassanzadeh, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced bladder cancer who are candidates for local therapy. They must use effective birth control and have adequate blood counts, kidney function, and an ECOG performance status of 0-2. Exclusions include significant prior treatment toxicity, HIV, certain immune conditions, uncontrolled diabetes or psychiatric disorders, distant metastases outside treatable areas by radiation, pregnancy or potential to conceive during the trial.

Inclusion Criteria

My doctor agrees I can have treatment aimed at curing my cancer.

I use reliable birth control methods.

I am using a reliable form of birth control.

Exclusion Criteria

I am experiencing side effects from previous cancer treatments.

I have been diagnosed with HIV.

I am not on high doses of steroids or immunosuppressants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin by vein on Days 1 and 8 of every 28-day cycle and radiation therapy 5 times a week for about 4-5 weeks

4-5 weeks

5 visits per week (in-person) for radiation, 2 visits per cycle (in-person) for enfortumab vedotin

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Radiation Therapy

Trial Overview The study tests if enfortumab vedotin combined with radiation can control locally advanced bladder cancer better than current treatments. Participants will receive both the drug and radiation therapy to see how well they work together against the disease.

How Is the Trial Designed?

Group I: Enfortumab Vedotin with Radiation Experimental Treatment 2 Interventions

Particpants will receive enfortumab vedotin by vein over about 1-2 hours on Days 1 and 8 of every 28-day cycle. Two dose levels of enfortumab vedotin will be tested. The dose of enfortumab vedotin participants receive will depend on when the participant join the study. Participants will also receive radiation therapy 5 times a week (Monday through Friday) for about 4-5 weeks.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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]

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]

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, 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]

Citations

1. 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.

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 ... After 5 years of follow-up in the Dose Escalation/Cohort A, EV+P continued to show durable responses and a meaningful survival, with a median OS ...

3. 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.

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. 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 ...