Pembrolizumab + EV for Bladder Cancer

Recruiting at 44 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Other malignancy, CNS metastases, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: Up to ~2 years

390 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new drug combinations to see if they work better than the current standard treatment for cancer patients. It focuses on patients treated with pembrolizumab plus EV. Pembrolizumab has shown effectiveness in various cancers, providing long-lasting responses and representing a major advancement in treatment options. The drugs aim to enhance the immune system's ability to fight cancer.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any other form of immunosuppressive therapy, you may need to stop these at least 7 days before the first dose of the study intervention.

What data supports the effectiveness of the drug combination of enfortumab vedotin and pembrolizumab for bladder cancer?

The combination of enfortumab vedotin and pembrolizumab has shown effectiveness in treating advanced bladder cancer, with enfortumab vedotin alone achieving a 44% response rate in patients who had previously received other treatments. This combination is being explored as a first-line treatment for patients who cannot receive cisplatin-based therapy. ^{1 2 3 4 5}

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

The combination of Enfortumab Vedotin and Pembrolizumab has been studied for bladder cancer, and while it shows promise, there are safety concerns. Serious side effects occurred in 73% of patients, including high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. ^{1 2 3 4 5}

What makes the drug combination of enfortumab vedotin and pembrolizumab unique for bladder cancer treatment?

This drug combination is unique because it offers a new first-line treatment option for patients with advanced bladder cancer who cannot receive cisplatin-based therapy, combining enfortumab vedotin, which targets cancer cells directly, with pembrolizumab, an immune therapy that helps the body’s immune system fight cancer. ^{1 2 3 4 6}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced bladder cancer that hasn't spread to the brain, who haven't had systemic therapy for it. They can have some other cancer types if they've been clear of them for 3+ years. No recent vaccines or investigational drugs, no immune diseases needing treatment in the last 2 years, and no active infections.

Inclusion Criteria

My cancer is mostly urothelial with little to no plasmacytoid component.

My cancer is an advanced bladder cancer confirmed by a biopsy.

I can provide a sample of my tumor for testing, either from a new biopsy or an existing sample.

Exclusion Criteria

I have an autoimmune disease but haven't needed systemic treatment in the last 2 years.

I have not had major surgery in the last 4 weeks.

I had another type of cancer but have been free of it for over 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab plus enfortumab vedotin (EV) with or without investigational agents in 3-week cycles for up to approximately 2 years

Up to ~2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to ~4 years

Treatment Details

Interventions

• Enfortumab Vedotin
• Pembrolizumab

Trial Overview The study tests how safe and effective new drug combos are: favezelimab/pembrolizumab plus EV, vibostolimab/pembrolizumab plus EV compared to just pembrolizumab plus EV. It's a two-part study where part one finds out which combo works best without comparing them directly.

Participant Groups

Group I: Arm B: Coformulated vibostolimab/pembrolizumab plus EV Experimental Treatment 2 Interventions

Participants will receive coformulated vibostolimab/pembrolizumab (200 mg/200 mg) as an IV infusion on Day 1 of every 3-week cycle, for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.

Group II: Arm A: Coformulated favezelimab/pembrolizumab plus EV Experimental Treatment 2 Interventions

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) as an intravenous (IV) infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.

Group III: Arm C: Pembrolizumab plus EV Active Control 2 Interventions

Participants will receive 200 mg pembrolizumab as an IV infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle, until disease progression, intolerable toxicity, or investigator decision.

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?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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]

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 (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 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 (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]

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

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

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

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

5. 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]

6. 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]