Enfortumab Vedotin + Pembrolizumab for Testicular and Urinary Tract Cancer

Overseen By Andrea B Apolo, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Neuropathy, CNS metastases, Autoimmune, 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

Compensation: Varies

Number of Visits: 7

Duration: Up to 5 years

68 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, enfortumab vedotin and pembrolizumab, in adults with rare testicle or urinary tract cancers. Enfortumab vedotin targets and kills cancer cells, while pembrolizumab boosts the immune system to fight the cancer. The goal is to see if this combination can help patients who have not responded to other treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic intravenous or oral corticosteroids or other immunosuppressive agents, these must be discontinued at least 1 week prior to treatment initiation for recent short-term use or at least 4 weeks prior for long-term use. Hormonal therapies for other cancers may be continued if stopping them could increase the risk of disease progression.

What data supports the effectiveness of the drug combination Enfortumab Vedotin and Pembrolizumab for testicular and urinary tract cancer?

Research shows that Enfortumab Vedotin and Pembrolizumab have been effective in treating advanced urothelial cancer, a type of urinary tract cancer, with significant response rates and survival benefits. This suggests potential effectiveness for similar cancers. ^{1 2 3 4 5}

Is the combination of Enfortumab Vedotin and Pembrolizumab safe for humans?

Enfortumab Vedotin has been associated with serious side effects, including high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. In studies, 73% of patients experienced severe side effects. These safety concerns are important to consider when evaluating this treatment. ^{1 2 3 5 6}

How is the drug combination of Enfortumab Vedotin and Pembrolizumab unique for testicular and urinary tract cancer?

This drug combination is unique because it combines Enfortumab Vedotin, an antibody-drug conjugate that targets cancer cells, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer. This combination has shown promise in treating advanced urothelial cancer, especially for patients who cannot use standard cisplatin-based therapies. ^{1 2 4 5 7}

Research Team

Andrea B Apolo, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with rare testicular or urinary tract cancers, including advanced adenocarcinoma and squamous cell carcinoma of the urinary tract, or refractory testicular germ cell tumors. Must have measurable disease and be in good physical condition (ECOG <=1). Some must have had prior anti-PD-1/PD-L1 therapy; others should not have received immune checkpoint inhibitors before. Women must agree to contraception use and discontinue breastfeeding.

Inclusion Criteria

Pre-study treatment tissue availability (sufficient tissue for 25 unstained slides) is mandatory for enrollment

My organs and bone marrow are functioning well.

Participants must be able to understand and willing to sign a written informed consent document

Exclusion Criteria

You have had serious allergic reactions to drugs similar to EV or pembrolizumab.

I have brain metastases that are causing symptoms or have not been treated.

Pregnant women as evaluated by a positive serum or urine beta-human chorionic gonadotropin (Beta-hCG) test at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive enfortumab vedotin with or without pembrolizumab in 21-day or 28-day cycles

Up to 5 years

3 visits per 28-day cycle or 2 visits per 21-day cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 to 4 weeks until disease progression, then every 3 months by phone

Open-label extension (optional)

Participants may continue to receive enfortumab vedotin for up to 5 years if they have completed 35 cycles of pembrolizumab

Up to 5 years

Treatment Details

Interventions

• Enfortumab Vedotin
• Pembrolizumab

Trial Overview The trial is testing Enfortumab Vedotin (EV), alone or combined with Pembrolizumab, for treating certain rare genitourinary cancers. Participants will receive treatments through an IV at varying intervals over cycles lasting several weeks, potentially continuing up to five years, accompanied by regular scans and tests.

Participant Groups

Group I: Arm 2 Experimental Treatment 2 Interventions

Treatment with enfortumab vedotin and pembrolizumab

Group II: Arm 1 Experimental Treatment 1 Intervention

Treatment with enfortumab vedotin

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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]

The combination of enfortumab vedotin (EV) and pembrolizumab (Pembro) demonstrated a high confirmed objective response rate (cORR) of 64.5% in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, indicating its efficacy as a first-line treatment option.

Patients receiving the combination therapy also experienced durable responses, with 65.4% maintaining their response at 12 months, while the safety profile showed manageable adverse events, with no new safety signals identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. O'Donnell, PH., Milowsky, MI., Petrylak, DP., et al.[2023]

Enfortumab vedotin (EV) and platinum rechallenge both demonstrated comparable oncological outcomes in patients with advanced urothelial carcinoma after prior treatments, with progression-free survival (PFS) and overall survival (OS) rates being similar between the two groups.

In a study of 64 patients, both treatments showed effective results, suggesting that EV can be a viable alternative to platinum rechallenge for patients who have already undergone platinum-based chemotherapy and pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study. Taguchi, S., Kawai, T., Ambe, Y., et al.[2023]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. [2023]

5. Australia pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]

7. United States 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. [2023]