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

Trial Summary

What is the purpose of this trial?

This study will test whether enfortumab vedotin combined with pembrolizumab is an effective treatment for people with bladder cancer (urothelial carcinoma) involving the lymph nodes who are going to have surgery to remove their cancer (cystectomy). The researchers will look at whether treatment with enfortumab vedotin and pembrolizumab before surgery can get rid of cancer within the lymph nodes. They will also try to find out if this combination of drugs is effective at shrinking participants' cancer before their surgery. The researchers think that a combination of enfortumab vedotin and pembrolizumab may help people with this disease because both drugs are designed to help the immune system attack and kill cancer cells. The researchers think the drugs may be more effective if given in combination rather than on their own.

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.

What data supports the effectiveness of the drug combination Enfortumab Vedotin and Pembrolizumab for bladder cancer?

Enfortumab Vedotin has been approved by the FDA for treating advanced bladder cancer after other treatments, showing a 44% response rate in patients. Both Enfortumab Vedotin and Pembrolizumab have shown benefits in treating bladder cancer, and their combination is being studied for further effectiveness. ^{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 a study, 73% of patients experienced severe side effects. Pembrolizumab, used in combination, also has its own safety profile, but specific safety data for the combination is not detailed in the available research. ^{1 2 3 4 6}

What makes the drug combination of Enfortumab Vedotin and Pembrolizumab unique for bladder cancer?

This drug combination is unique because it combines Enfortumab Vedotin, a first-in-class antibody-drug conjugate targeting Nectin-4, with Pembrolizumab, an immune checkpoint inhibitor, to treat advanced bladder cancer. This approach is novel as it targets cancer cells directly while also boosting the immune system to fight the cancer, offering a new option for patients who have already received other treatments. ^{1 2 3 4 6}

Research Team

David Aggen, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

I can carry out all my daily activities without help.

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

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

Treatment Details

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.

Participant Groups

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

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 (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]

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]

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]

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

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

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

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

5. 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]

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]