Pembrolizumab + EV for Bladder Cancer

Not currently recruiting at 56 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for advanced bladder cancer. Researchers are testing the effectiveness of different drug combinations with enfortumab vedotin (EV), a medication already used for bladder cancer. The trial includes three groups: two groups will receive different combinations of pembrolizumab with either favezelimab or vibostolimab, plus EV, while one group will receive pembrolizumab plus EV only. Individuals with bladder cancer that has spread or cannot be removed by surgery, and who have not received systemic treatment for this condition, might be suitable candidates. The goal is to determine which combination is the safest and most effective for treating bladder cancer. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

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

Research shows that the combination of enfortumab vedotin and pembrolizumab has been studied for bladder cancer and has shown promising results. However, previous studies have reported serious side effects, raising safety concerns. Although the FDA has approved this combination for certain advanced cancers, suggesting some level of safety, it still carries risks.

This trial tests new combinations of treatments: favezelimab and vibostolimab combined with pembrolizumab and enfortumab vedotin. Past studies provide limited specific safety information about these new combinations. As this trial is in the early stages, it focuses on understanding safety and determining the right dosage. Researchers are still assessing how well participants tolerate these treatments. Participants should consider that while there is potential, the exact safety profile is still under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they explore innovative combinations that could offer improved outcomes. Unlike the standard of care, which often involves chemotherapy or immunotherapy alone, these trial arms combine pembrolizumab with other agents like enfortumab vedotin (EV), favezelimab, and vibostolimab. Pembrolizumab is a well-known immunotherapy that boosts the body's immune response against cancer cells. Enfortumab vedotin is an antibody-drug conjugate specifically targeting cancer cells to deliver a toxic payload. Favezelimab and vibostolimab are newer immune checkpoint inhibitors that might enhance the effects of pembrolizumab. By combining these drugs, researchers hope to attack the cancer from multiple angles, potentially leading to more effective treatment options.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that the drugs enfortumab vedotin (EV) and pembrolizumab effectively treat bladder cancer, especially when other treatments have failed. Studies have found that using these two drugs together can significantly increase survival rates, doubling the chances compared to chemotherapy. Specifically, the combination of pembrolizumab and EV, which participants in this trial may receive, demonstrated better overall survival and longer periods without disease progression in advanced bladder cancer. This trial will also test combinations of favezelimab/pembrolizumab plus EV and vibostolimab/pembrolizumab plus EV, hoping they will be as successful as pembrolizumab and EV. Overall, current data suggests these treatments are promising for bladder cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 am currently being treated for an active infection.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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 (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 (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-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]

Citations

1. merck.com merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-significantly-improved-event-free-and-overall-survival-and-pathologic-complete-response-rate-for-certain-patients-with-muscle/

KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab ... In this study, KEYTRUDA® (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv), given before and after surgery (radical cystectomy), ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12051594/

Enfortumab vedotin and pembrolizumab Both EV and pembrolizumab have previously individually shown to be effective in bladder cancer after other treatments have failed. In a large study including ...

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-enfortumab-vedotin-ejfv-pembrolizumab-locally-advanced-or-metastatic-urothelial-cancer

FDA approves enfortumab vedotin-ejfv with ... The major efficacy outcome measures were overall survival (OS) and progression-free survival (PFS) as assessed by blinded independent central ...

4. pfizer.com pfizer.com/news/press-release/press-release-detail/padcevr-enfortumab-vedotin-ejfv-keytrudar-pembrolizumab

PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® ... “In the Phase 3 EV-302 study, the combination of PADCEV and pembrolizumab demonstrated survival benefit for patients with advanced bladder ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-5-2023-3cc11

Pembrolizumab + EV for Bladder Cancer The combination of enfortumab vedotin and pembrolizumab has shown effectiveness in treating advanced bladder cancer, with enfortumab vedotin alone achieving a ...