Pembrolizumab + Enfortumab Vedotin for Urothelial Carcinoma

Recruiting in Palo Alto (17 mi)

Overseen by Karim Chamie, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Antidepressants, Immunosuppressants, others

Disqualifiers: Pregnancy, Autoimmune disease, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II clinical trial tests how well pembrolizumab plus enfortumab vedotin prior to and after radical nephroureterectomy works in treating patients with high-risk upper tract urothelial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Enfortumab vedotin (EV) is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Radical nephroureterectomy (RNU) is the surgical removal of a kidney and its ureter. Giving pembrolizumab plus enfortumab vedotin before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed and giving pembrolizumab after surgery may kill any remaining cancer cells.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received certain cancer therapies or live vaccines recently, and should not be on high-dose steroids or immunosuppressive therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Pembrolizumab and Enfortumab Vedotin for treating urothelial carcinoma?

The FDA approved Enfortumab Vedotin for treating advanced urothelial cancer after other treatments, showing a 44% response rate in a study. Additionally, a case report showed a complete response in a patient using Enfortumab Vedotin after other treatments, suggesting its potential effectiveness. ^{1 2 3 4 5}

How is the drug combination of Pembrolizumab and Enfortumab Vedotin unique for treating urothelial carcinoma?

This drug combination is unique because it combines Pembrolizumab, an immunotherapy that helps the immune system attack cancer cells, with Enfortumab Vedotin, an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, potentially enhancing effectiveness and reducing side effects compared to traditional chemotherapy. ^{6 7 8 9 10}

Research Team

Karim Chamie, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

Adults with high-risk upper tract urothelial cancer can join this trial. They must have proper kidney function, normal blood counts, and be in good physical condition (ECOG 0-1). Women should not be pregnant or breastfeeding and must follow contraceptive guidance. Men also need to use contraception. Participants cannot have had certain treatments recently, other active cancers, severe allergies to the drugs being tested, or any immune system problems.

Inclusion Criteria

Participants must meet specified laboratory values within 10 days prior to study intervention

I am 18 or older with a confirmed high-risk upper tract urothelial carcinoma diagnosis.

I can provide a sample of my tumor, either from previous or new biopsy.

Exclusion Criteria

I have a history of Hepatitis B or active Hepatitis C.

Active autoimmune disease requiring systemic treatment in the past 2 years

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab and enfortumab vedotin intravenously before radical nephroureterectomy

8-12 weeks

Multiple visits for IV administration

Surgery

Participants undergo radical nephroureterectomy

1 day

1 visit (in-person)

Adjuvant Treatment

Participants receive pembrolizumab intravenously after surgery

up to 1 year

Regular visits for IV administration

Follow-up

Participants are monitored for safety, effectiveness, and recurrence after treatment

up to 3 years

Regular follow-up visits

Treatment Details

Interventions

• Enfortumab Vedotin (Antibody-drug Conjugate)
• Nephroureterectomy (Surgery)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The trial is testing if combining pembrolizumab (an immunotherapy drug) with enfortumab vedotin (a targeted therapy) before and after surgical removal of a kidney and ureter can better treat patients. Pembrolizumab boosts the immune system's response against cancer cells while enfortumab vedotin delivers a toxin directly to them.

Participant Groups

Group I: Treatment (pembrolizumab, enfortumab vedotin) Experimental Treatment 6 Interventions

Patients receive pembrolizumab IV and enfortumab vedotin IV on study. Patients undergo radical nephroureterectomy and receive pembrolizumab IV on study Patients also undergo MRU imaging and undergo blood, urine and tissue sample collection throughout the study.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UCLA / Jonsson Comprehensive Cancer Center Los Angeles, CA

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Patients Recruited

35,200+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4096

Patients Recruited

5,232,000+

Seagen Inc.

Industry Sponsor

Trials

212

Patients Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

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]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Response to Enfortumab Vedotin in a Hemodialysis Patient with Metastatic Urothelial Carcinoma: A Case Report. Isoda, B., Shiga, M., Kandori, S., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Fellström, BC., Barratt, J., Cook, H., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience of a Performance-Based Risk-Sharing Arrangement for the Treatment of Rheumatoid Arthritis With Certolizumab Pegol. Di Giuseppe, LA., Buela, G., Zacariaz Hereter, JB., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. Cheng, G., Liu, D., Margetts, P., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of leflunomide in the treatment of polyomavirus BK-associated nephropathy. Wu, JK., Harris, MT.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of leflunomide combined with hormone therapy for refractory IgA nephropathy]. Rong, L., Liu, ZR.[2018]

References

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

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

2. 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]

3. 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]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Complete Response to Enfortumab Vedotin in a Hemodialysis Patient with Metastatic Urothelial Carcinoma: A Case Report. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. [2022]

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

Experience of a Performance-Based Risk-Sharing Arrangement for the Treatment of Rheumatoid Arthritis With Certolizumab Pegol. [2021]

8. Australia pubmed.ncbi.nlm.nih.gov

Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. [2018]

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

Use of leflunomide in the treatment of polyomavirus BK-associated nephropathy. [2018]

10. China pubmed.ncbi.nlm.nih.gov

[Effects of leflunomide combined with hormone therapy for refractory IgA nephropathy]. [2018]