70 Participants Needed

Enfortumab Vedotin + Pembrolizumab for Bladder Cancer

RR
Overseen ByRyan Romasko
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different treatment plans for advanced bladder cancer. One group receives enfortumab vedotin (an antibody-drug conjugate) alone, while the other receives a combination of enfortumab vedotin and pembrolizumab (an immunotherapy drug). The goal is to determine if altering the frequency of these drugs can better control the cancer. The trial seeks participants with advanced bladder cancer who have completed other treatments and have measurable cancer on scans. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires that any prior systemic therapy must be completed at least 14 days before starting the study treatment. However, the protocol does not specify if you need to stop other current medications, so it's best to discuss this with the study team.

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

Research has shown that Enfortumab Vedotin, when used alone, is approved for treating advanced bladder cancer after other treatments have failed. This indicates it has undergone safety testing in people. Some patients experience side effects like tiredness and skin rash, but it is generally well-tolerated.

Studies have also shown that the combination of Enfortumab Vedotin with Pembrolizumab is approved for treating advanced bladder cancer. This suggests that using both drugs together is considered safe. Patients have reported side effects such as tiredness and nausea, which are common with cancer treatments.

Since this trial is in an early stage, it aims to further confirm the effectiveness and safety of these treatments. Participants should be aware that while previous data shows the treatments are generally safe, risks may still exist.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about enfortumab vedotin and pembrolizumab for bladder cancer because these treatments introduce a fresh approach compared to standard options like chemotherapy or immune checkpoint inhibitors alone. Enfortumab vedotin is an antibody-drug conjugate that specifically targets and delivers chemotherapy to cancer cells, potentially reducing side effects and increasing effectiveness. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. When used together, they may offer a more powerful one-two punch against bladder cancer, potentially leading to better outcomes 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 as monotherapy, can help people with advanced bladder cancer live longer. In one study, 4.9% of patients experienced complete cancer remission, and 35.8% saw their cancer shrink. Another group in this trial will receive enfortumab vedotin combined with pembrolizumab. This combination lowered the risk of death by 49% compared to standard chemotherapy. Another study found that this combination works better than chemotherapy alone for those not yet treated for advanced cancer. These findings suggest that using enfortumab vedotin alone or with pembrolizumab can effectively treat bladder cancer.23678

Who Is on the Research Team?

PG

Pooja Ghatalia, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced or metastatic urothelial cancer, who have measurable disease and are planning to receive Enfortumab Vedotin (EV) as standard treatment. They must be over 18, have finished any prior systemic therapy at least two weeks before, and be in a fair to good physical state (ECOG 0-2). Participants need normal organ/marrow function and must provide a tumor tissue sample if available.

Inclusion Criteria

My blood counts and kidney and liver functions are within normal ranges.
My cancer tissue sample is available for testing.
My bladder cancer is advanced or has spread, confirmed by tests.
See 6 more

Exclusion Criteria

I have been treated with MMAE-based drugs for bladder cancer.
I have a history of lung scarring or inflammation not caused by infections.
I have moderate to severe numbness, tingling, or muscle weakness.
See 10 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Enfortumab Vedotin (EV) monotherapy or EV in combination with pembrolizumab. EV monotherapy is administered at a standard dose of 1.25 mg/kg IV on days 1, 8, and 15 of a 28-day cycle for 3 cycles. EV/pembrolizumab is administered with EV at a standard dose of 1.25 mg/kg IV on days 1 and 8, and pembrolizumab 200 mg IV on day 1 of a 21-day cycle for 6 cycles.

12-18 weeks

Schedule De-escalation

First schedule de-escalation occurs for patients with disease control at 12 weeks for EV monotherapy and at 9 weeks for EV/pembrolizumab. Second schedule de-escalation occurs at 24 weeks for EV monotherapy.

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Overall survival and time to next treatment are assessed over a 5-year period.

5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Enfortumab Vedotin
  • Pembrolizumab
Trial Overview The trial is testing an alternative schedule for administering EV alone and in combination with Pembrolizumab in patients with advanced urothelial cancer. It's an open-label phase 2 study, meaning both researchers and participants know what treatments are given.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: EV/pembrolizumabExperimental Treatment2 Interventions
Group II: Enfortumab vedotin (EV) monotherapyActive Control1 Intervention

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

🇺🇸
Approved in United States as Padcev for:
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Approved in European Union as Padcev for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials
236
Recruited
39,300+

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

Citations

KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab ...KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab vedotin-ejfv) Significantly Improved Event-Free and Overall Survival and Pathologic Complete ...
PADCEV™ Plus KEYTRUDA™ Significantly Improves ...PADCEV plus KEYTRUDA is the first and only regimen to improve survival when used before and after standard of care (surgical cystectomy) in ...
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 ...
4.pubmed.ncbi.nlm.nih.govpubmed.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 ...
1L PADCEV + Pembrolizumab Efficacy - Enfortumab vedotinGraph showing 31.5 months median overall survival with PADCEV + pembrolizumab and 16.1 months median overall. The median survival follow-up time was 17.2 months ...
Padcev - accessdata.fda.govNonclinical 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 ...
Enfortumab vedotin and pembrolizumabThe combination of enfortumab vedotin and pembrolizumab is the new recommended treatment for locally advanced and metastatic urothelial cancer.
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.
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