Enfortumab Vedotin + Pembrolizumab for Bladder Cancer

(KEYNOTE-B15 Trial)

Recruiting at 249 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: PD-1 inhibitors

Disqualifiers: Metastatic disease, HIV, Hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

808 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for bladder cancer to determine if they outperform current standard treatments. It compares enfortumab vedotin (EV) and pembrolizumab (a type of immunotherapy) combined with surgery to traditional chemotherapy and surgery. The goal is to discover if this new approach can extend life without cancer recurrence. People with muscle-invasive bladder cancer who haven't received certain treatments before and are eligible for surgery might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants should not have received certain cancer treatments or vaccines recently, so it's best to discuss your specific medications with the trial team.

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 safe. In a study with 442 patients, most side effects were manageable. The treatment improved outcomes, and serious side effects were rare, with benefits often outweighing risks.

Another study found that this combination outperformed chemotherapy for bladder cancer patients. This indicates that the treatment is both effective and has an acceptable safety level for most patients.

Overall, while side effects can occur, they are usually not severe. These findings can reassure prospective trial participants about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Enfortumab Vedotin (EV) and Pembrolizumab for bladder cancer because it offers a novel approach compared to the standard treatment. Unlike traditional chemotherapy options like gemcitabine and cisplatin, EV is an antibody-drug conjugate that specifically targets and delivers a potent chemotherapy agent directly to cancer cells, minimizing damage to healthy cells. Pembrolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells. This dual-action strategy not only aims to improve the precision of treatment but also enhances the body's natural defenses against the cancer, potentially leading to better outcomes and fewer side effects.

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

Research shows that combining enfortumab vedotin with pembrolizumab holds promise for treating bladder cancer. In this trial, one group of participants will receive this combination. Studies have found that this combination significantly extends the lives of patients with muscle-invasive bladder cancer. Specifically, patients lived an average of 26.7 months with this treatment, compared to 14.9 months with enfortumab vedotin alone. Additionally, 68% of patients experienced tumor reduction or disappearance when these drugs were used together. These findings suggest that enfortumab vedotin plus pembrolizumab could effectively improve survival and response rates in bladder cancer patients. ^{1 4 6 7 8}

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 muscle invasive bladder cancer (MIBC) that's not spread beyond the lymph nodes. They must have mostly urothelial cancer, be fit for surgery to remove the bladder and nearby lymph nodes, and have good organ function. People can't join if they've had certain cancers or treatments in the last 3 years, live vaccines recently, HIV/Hepatitis B/C infections, severe neuropathy or eye issues, uncontrolled diabetes, are ineligible for cisplatin chemotherapy or have more advanced cancer.

Inclusion Criteria

My organs are functioning well.

My bladder cancer has not spread beyond my pelvis.

I am considered a candidate for surgery to remove my bladder and nearby lymph nodes.

Exclusion Criteria

I have had cancer treatment or been in a cancer study within the last 3 years.

I cannot receive cisplatin due to specific health reasons.

I have another cancer besides the one being studied, but it hasn't needed treatment in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 cycles of either perioperative enfortumab vedotin plus pembrolizumab or neoadjuvant chemotherapy (gemcitabine plus cisplatin) followed by radical cystectomy and pelvic lymph node dissection

3 months

Adjuvant Treatment

Participants in the experimental arm receive 5 cycles of adjuvant enfortumab vedotin and 13 cycles of adjuvant pembrolizumab postoperatively

9 months

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after treatment

Up to 68 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Enfortumab vedotin (EV)
• Gemcitabine
• Pembrolizumab
• Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)

Trial Overview The study compares two approaches before and after bladder removal surgery: one group gets a drug combo of Enfortumab Vedotin plus Pembrolizumab; another receives standard chemo with Gemcitabine plus Cisplatin. The goal is to see which method keeps patients free from cancer events longer.

How Is the Trial Designed?

Group I: Arm A: Perioperative EV+ Pembrolizumab and RC + PLND Experimental Treatment 3 Interventions

Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.

Group II: Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND Active Control 3 Interventions

Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

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

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

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

Published Research Related to This Trial

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]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

In a study of 45 cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, the combination of enfortumab vedotin and pembrolizumab resulted in a high confirmed objective response rate of 73.3%, indicating significant tumor shrinkage.

The treatment demonstrated a manageable safety profile, with most adverse events being manageable, and showed promising median durations of response and overall survival of 25.6 months and 26.1 months, respectively, suggesting its potential as an effective first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. 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]

In a phase 2 study involving 91 patients with locally advanced or metastatic urothelial carcinoma who were ineligible for cisplatin and had previously received PD-1 or PD-L1 therapy, enfortumab vedotin demonstrated a confirmed objective response rate of 52%, indicating significant efficacy in this difficult-to-treat population.

While enfortumab vedotin was generally tolerable, 55% of patients experienced grade 3 or worse treatment-related adverse events, highlighting the need for careful monitoring, especially since some serious adverse events, including treatment-related deaths, were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial. Yu, EY., Petrylak, DP., O'Donnell, PH., 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4576

Assessing treatment outcomes of enfortumab vedotin dose ... Our single center, retrospective study, aims to assess the impact of EV dose reduction on treatment duration, AEs, and survival.

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. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2831221

Enfortumab Vedotin With or Without Pembrolizumab in ... The findings suggest that enfortumab vedotin, especially combined with pembrolizumab, offers promising beneficial outcomes in metastatic urothelial carcinoma ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842825003336

Survival outcomes with enfortumab vedotin–containing ... Median overall survival with EV alone was 14.9 months, which increased to 26.7 months with EV+pembrolizumab. •. The objective response rate was 68 % for the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12173200/

Optimizing enfortumab vedotin plus pembrolizumab therapy Initial efficacy, supported by early phase II clinical trials, included an ORR of 40% and a median OS of 11 months [39]. Furthermore, in the ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.664

EV-302: Updated analysis from the phase 3 global study of ... An exploratory analysis evaluated treatment outcomes and safety in pts with cCR. Results: 886 pts were randomized to receive EV+P (n=442) or ...

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

Enfortumab Vedotin and Pembrolizumab in Untreated ... Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or ...

8. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-press-releases/164072-keytruda-r-pembrolizumab-plus-padcev-r-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-cancer-when-given-before-and-after-surgery.html

Pembrolizumab Plus Enfortumab Vedotin-ejfv Reduced ... The pCR rate increased from 8.6% in patients treated with surgery alone (n=15/174) to 57.1% in patients treated with perioperative KEYTRUDA plus Padcev (n=97/ ...