Enfortumab Vedotin for Pancreatic Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Steroids, Antimicrobials

Disqualifiers: CNS metastases, Active infections, Uncontrolled diabetes, 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

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

Compensation: Varies

Number of Visits: 4

Duration: Approximately 2 years or until disease progression

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Enfortumab Vedotin, an antibody-drug conjugate, for individuals with advanced pancreatic cancer that has worsened after previous treatments. The main goal is to determine how effectively this treatment controls the cancer and improves patients' health. Those who have battled pancreatic cancer and found other treatments unsuccessful might be suitable for this trial. Participants will receive Enfortumab Vedotin through an IV on specific days each month. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use other cancer treatments or investigational drugs while participating. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that Enfortumab Vedotin is likely to be safe for humans?

Research has shown that enfortumab vedotin is already approved for treating advanced bladder cancer. In studies with these patients, 64.5% responded to the treatment, with many experiencing a reduction in cancer size or halted growth. The treatment is generally well-tolerated, though, like any medication, it can cause side effects. Common side effects include fatigue, skin rash, and changes in blood sugar levels. More serious side effects are less common but may include nerve damage or skin reactions.

These findings suggest that while enfortumab vedotin has been effective and generally safe in treating other cancers, participants should discuss potential risks with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Enfortumab vedotin is unique because it targets a protein called Nectin-4, which is often found on the surface of pancreatic cancer cells. This is different from standard treatments like chemotherapy, which attack rapidly dividing cells more generally. Enfortumab vedotin is an antibody-drug conjugate, meaning it combines an antibody with a cancer-killing drug, delivering the drug directly to the cancer cells while sparing healthy ones. Researchers are excited about this treatment because it offers a more precise way to target and destroy cancer cells, potentially leading to fewer side effects and improved outcomes for patients.

What evidence suggests that Enfortumab Vedotin might be an effective treatment for pancreatic cancer?

Research has shown that enfortumab vedotin, the treatment under study in this trial, may help treat certain cancers. In an earlier study on pancreatic cancer, 44% of patients experienced tumor shrinkage, with this effect lasting about 7.6 months on average. However, 73% of patients experienced significant side effects. Although enfortumab vedotin is more commonly used for bladder cancer, these early results for pancreatic cancer appear promising. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced pancreatic cancer who've had previous treatment. They must have good kidney and liver function, no major recent heart issues or active infections, and can't be on other clinical trials. Women of childbearing age need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

Your liver enzymes (AST and ALT) should not be too high, unless you have cancer that has spread to the liver, in which case they can be a little higher.

Your bilirubin levels in the blood are within a certain range.

My kidney function, measured by creatinine levels, is within the normal range.

Exclusion Criteria

Has a known allergic reaction to any excipient contained in the study drug formulation

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

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Enfortumab vedotin, 1.25 mg/kg IV on Days 1, 8, 15 every 28 days

Approximately 2 years or until disease progression

Visits on Days 1, 8, 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin

Trial Overview The study tests Enfortumab Vedotin in patients with advanced pancreatic cancer that has worsened despite treatment. It's an open-label Phase II trial, meaning everyone knows they're getting the drug, not a placebo.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Enfortumab vedotin, 1.25 mg/kg IV on D 1,8,15 every 28 days

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 Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

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]

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 option for adults with locally advanced or metastatic urothelial carcinoma who have already received PD-1/PD-L1 inhibitors and platinum-based chemotherapy, as it targets the Nectin-4 protein.

To maximize the benefits of EV therapy, it is crucial to educate patients and caregivers, monitor for adverse events, and intervene promptly to manage any side effects that may arise during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. Pace, A., Brower, B., Conway, D., et al.[2021]

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 subgroup analysis of 86 Japanese patients with locally advanced or metastatic urothelial carcinoma, enfortumab vedotin (EV) demonstrated a median overall survival of 15.18 months, significantly longer than the 10.55 months observed with standard chemotherapy.

EV also showed a higher confirmed overall response rate (34.4%) compared to standard chemotherapy (21.3%), while having a lower incidence of treatment-related adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Japanese subgroup analysis of EV-301: An open-label, randomized phase 3 study to evaluate enfortumab vedotin versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial carcinoma. Matsubara, N., Yonese, J., Kojima, T., et al.[2023]

Citations

1. padcev.com padcev.com/trial-results

Clinical Study Results | PADCEV® (enfortumab vedotin-ejfv) Results from PADCEV clinical studies. PADCEV was studied in adults with advanced bladder cancer or cancers of the urinary tract.

2. withpower.com withpower.com/trial/phase-2-adenocarcinoma-5-2023-039b5

Enfortumab Vedotin for Pancreatic Cancer 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 ...

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. merck.com merck.com/news/seagen-astellas-and-merck-announce-results-of-clinical-trial-investigating-padcev-enfortumab-vedotin-ejfv-with-keytruda-pembrolizumab-and-padcev-as-monotherapy-in-first-line-advanced/

Seagen, Astellas and Merck Announce Results of Clinical ... Results demonstrated a 64.5% confirmed objective response rate in patients treated with investigational combination of enfortumab vedotin and pembrolizumab.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7494003/

Therapeutic Potential of Enfortumab Vedotin - PMC The ORR was 43%, with 5 subjects (4.5%) achieving complete remission (CR), and the median duration of response (DOR) was 7.4 months (95% CI, 5.6 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12486332/

Treatment‐Related Adverse Events and Associated Outcomes ... Enfortumab vedotin‐ejfv (EV) is an approved therapy for advanced urothelial carcinoma (aUC), but real‐world safety data remain limited. In the ...

7. 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 ...