Enfortumab Vedotin + Pembrolizumab for Bladder Cancer

Recruiting at 15 trial locations

Overseen By Jonathan Rosenberg, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antidepressants, Steroids, Antibiotics, others

Disqualifiers: Heart disease, Diabetes, 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: 17

Duration: 18 weeks

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of two drugs, enfortumab vedotin (an antibody-drug conjugate) and pembrolizumab (an immunotherapy), can effectively treat bladder cancer that has spread to the lymph nodes in patients planning to undergo surgery. These drugs help the immune system target and kill cancer cells. The trial will assess whether this treatment can clear cancer from the lymph nodes and shrink tumors before surgery. Individuals with muscle-invasive bladder cancer involving the lymph nodes, who have not received prior treatments for this condition, may be a good fit for this trial.

As a Phase 2 trial, the research focuses on measuring how well the treatment works in an initial, smaller group of people, offering a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. However, it does mention that participants should not be on certain treatments like systemic anti-cancer therapy or live vaccines shortly before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

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

Research has shown that the combination of enfortumab vedotin and pembrolizumab is generally well-tolerated by patients with advanced bladder cancer. Studies have found that this combination can improve survival chances compared to traditional chemotherapy. However, side effects can occur with any treatment. Common side effects include fatigue, skin rash, and changes in blood cell levels. Serious side effects can occur but are less common. Patients should discuss with their doctor to understand what this might mean for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Enfortumab Vedotin and Pembrolizumab for bladder cancer because it brings together two powerful approaches. Enfortumab Vedotin is an antibody-drug conjugate that specifically targets cancer cells and delivers a toxic payload to kill them, while Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells. This dual approach not only aims to shrink tumors more effectively but also helps the body’s own defenses keep fighting cancer after the initial treatment. Unlike traditional chemotherapy, which can damage healthy cells, this combination is more targeted, potentially leading to fewer side effects and better outcomes for patients.

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

Participants in this trial will receive a combination of enfortumab vedotin and pembrolizumab. Studies have shown that this combination can significantly improve survival for patients with muscle-invasive bladder cancer. It has extended both event-free survival and overall survival. In one study, patients receiving this treatment lived a median of 31.5 months, compared to 16.1 months for those who did not. This suggests that the combination effectively reduces cancer in the lymph nodes and shrinks tumors before surgery. The treatment enhances the immune system's ability to attack and destroy cancer cells. ^{2 3 6 7 8}

Who Is on the Research Team?

David Aggen, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with muscle invasive bladder cancer who are fit for surgery to remove their cancer. They must have no prior treatments for advanced urothelial carcinoma, be eligible for platinum-based chemotherapy, and have an ECOG performance status of 0-1 (which means they are fully active or restricted in physically strenuous activity but can do light work). Participants need functioning major organs and agree to use contraception.

Inclusion Criteria

I can carry out all my daily activities without help.

Patients willing and able to provide written informed consent for the trial

I am 18 or older with a confirmed diagnosis of muscle invasive bladder cancer.

Exclusion Criteria

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

I have had treatments for bladder cancer before.

I am of childbearing age and my pregnancy test is positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin and pembrolizumab for up to 6 cycles, with imaging assessments after 3 and 6 cycles, followed by cystectomy

18 weeks

6 visits (in-person) for drug administration, imaging assessments after 3 and 6 cycles

Surgery

Participants undergo cystectomy to remove cancer

4-8 weeks post-treatment

Follow-up

Participants resume pembrolizumab monotherapy for an additional 11 doses to complete 1 year of therapy

33 weeks

11 visits (in-person) for pembrolizumab administration

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Pembrolizumab

Trial Overview The study tests if enfortumab vedotin combined with pembrolizumab before surgery can eliminate lymph node cancer and shrink tumors in patients with bladder cancer. It explores whether these drugs, which boost the immune system's ability to kill cancer cells, work better together than alone.

How Is the Trial Designed?

Group I: enfortumab vedotin in combination with pembrolizumab Experimental Treatment 2 Interventions

Enfortumab vedotin will be administered at 1.25 mg/kg on day 1 and day 8 of each 21-day cycle, for up to 6 cycles. Patients can proceed to surgery prior to completion of cycle 6 at the discretion of the investigator and urologist if toxicities prevent completion of 6 cycles of treatment. Enfortumab vedotin will be capped at a maximum dose of 125 mg for each infusion (for patients who weigh \> 100 kg). Pembrolizumab will be administered on day 1 of each cycle, every 21 days, for 6 cycles. After completion of 3 cycles patients with have imaging assessment, and patients with progression of disease as measured by distant metastases will be removed from the study. At completion of cycle 6, patients will have repeat imaging assessment and proceed to cystectomy within 4-8 weeks. Following cystectomy, patients will resume pembrolizumab monotherapy on day 1 of each 21-day cycle for an additional 11 doses (Cycles 7-17), to complete 1 year of pembrolizumab therapy.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Astellas Pharma US, Inc.

Industry Sponsor

Trials

90

Recruited

12,900+

Naoki Okamura

Astellas Pharma US, Inc.

Chief Executive Officer since 2023

Not available

Tadaaki Taniguchi

Astellas Pharma US, Inc.

Chief Medical Officer since 2023

MD, PhD

Seagen Inc.

Industry Sponsor

Trials

212

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)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Merck Sharp & Dohme LLC

Industry 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) 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]

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-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]

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]

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 ... The trial is continuing to evaluate the secondary EFS, OS, and pCR rate endpoints for neoadjuvant and adjuvant KEYTRUDA versus surgery alone as ...

2. onclive.com onclive.com/view/perioperative-enfortumab-vedotin-plus-pembrolizumab-displays-positive-topline-data-in-muscle-invasive-bladder-cancer

Perioperative Enfortumab Vedotin Plus Pembrolizumab ... Enfortumab vedotin plus pembrolizumab significantly improved survival outcomes in patients with muscle-invasive bladder cancer who were ...

3. padcev.com padcev.com/trial-results

Clinical Study Results | PADCEV® (enfortumab vedotin-ejfv) See clinical study data for PADCEV® in adults with advanced bladder cancer or cancers of the urinary tract. See full PI, including Serious Side Effects.

4. pfizer.com pfizer.com/news/press-release/press-release-detail/padcevtm-plus-keytrudatm-significantly-improves-survival

PADCEV™ Plus KEYTRUDA™ Significantly Improves ... PADCEV plus KEYTRUDA is the first and only regimen to improve survival when used before and after standard of care (surgical cystectomy) in ...

5. padcevhcp.com padcevhcp.com/padcev-pembrolizumab-efficacy

1L PADCEV + Pembrolizumab Efficacy - Enfortumab vedotin Graph showing 31.5 months median overall survival with PADCEV + pembrolizumab and 16.1 months median overall. The median survival follow-up time was 17.2 months ...

6. merck.com merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-reduced-risk-of-event-free-survival-events-by-60-and-risk-of-death-by-50-for-certain-patients-with-muscle-invasive-bladder-ca/

KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab ... KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Event-Free Survival Events by 60% and Risk of Death by 50% for Certain Patients ...

7. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-and-astellas-padcevr-enfortumab-vedotin-ejfv-plus-0

Pfizer and Astellas' PADCEV® (enfortumab vedotin-ejfv) ... Enfortumab vedotin plus pembrolizumab continues to demonstrate superior efficacy versus chemotherapy in a broad population, reinforcing the ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38446675/

Enfortumab Vedotin and Pembrolizumab in Untreated ... Conclusions: Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with ...