Pembrolizumab for Bladder Cancer

Not currently recruiting at 3 trial locations

Overseen By Matthew D Galsky, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vaibhav Patel

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Prior chemotherapy, Active infection, Hepatitis, HIV, 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)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of pembrolizumab, a type of immunotherapy, in treating bladder cancer that has invaded the muscle but remains confined to the bladder area. Participants will first receive pembrolizumab, and researchers will assess their cancer's response. If the cancer shrinks or disappears, pembrolizumab treatment will continue; if not, participants will receive standard treatments such as surgery or radiation, followed by additional pembrolizumab. The study seeks individuals with bladder cancer that has not spread to lymph nodes or other organs, who are ineligible for certain chemotherapy treatments, and have undergone a specific type of tumor removal surgery. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you are on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study drug. It's best to discuss your current medications with the trial team.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research shows that pembrolizumab, a treatment tested for bladder cancer, is generally well-tolerated. Previous studies have found that its side effects align with known effects, with no new unexpected side effects appearing.

In one study, pembrolizumab was combined with another treatment, and the safety profile remained similar to each treatment used alone. This indicates that pembrolizumab does not introduce new risks when combined with other medicines.

Pembrolizumab has been tested in many patients with bladder cancer and other types of cancer. The FDA has already approved it for other conditions, suggesting a good safety record. While side effects can occur, they are usually manageable. Always consult a healthcare provider about what to expect and any concerns about joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Pembrolizumab is unique because it harnesses the power of the immune system to fight bladder cancer by blocking the PD-1 pathway, a mechanism that tumors use to hide from immune attacks. Unlike standard treatments such as surgery, chemotherapy, or radiation, which directly target the cancer cells, pembrolizumab enhances the body's natural defenses to identify and destroy cancer cells. Researchers are excited about pembrolizumab because it offers a promising alternative for patients who may not respond well to conventional therapies, potentially leading to improved outcomes and longer-lasting remissions.

What evidence suggests that pembrolizumab might be an effective treatment for bladder cancer?

Research has shown that pembrolizumab holds promise for treating bladder cancer. In previous studies, it extended survival, with about 61% of patients still alive three years post-treatment. Another study found that pembrolizumab was effective in 29% of patients, as their tumors shrank or disappeared. It also prolonged the time patients lived without cancer recurrence. In this trial, participants will receive pembrolizumab as part of the experimental group, which may include maintenance or adjuvant therapy following standard local therapy. These findings suggest that pembrolizumab could be effective for people with bladder cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Matthew Galsky, M.D.

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults with muscle-invasive urothelial bladder cancer (cT2-T3N0M0) who haven't had systemic chemotherapy or radiation for it, can decline or are ineligible for cisplatin-based chemo due to certain health conditions. They must have adequate organ function and agree to use contraception. Excluded if pregnant, breastfeeding, recently vaccinated with live vaccines, have active infections or other health issues that could affect the trial.

Inclusion Criteria

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

ECOG Performance Status of ≤ 1 within 28 days prior to registration.

You have bladder cancer that has not spread to other parts of the body and specific criteria regarding the size of lymph nodes on imaging.

Exclusion Criteria

You have received radiation therapy for bladder cancer before.

Has a known history of active TB (Bacillus Tuberculosis).

Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two cycles of pembrolizumab, followed by restaging MRI, CT, cystoscopy, and biopsies

12 weeks

Multiple visits for treatment and restaging assessments

Maintenance or Adjuvant Treatment

Participants achieving a clinical complete response receive maintenance pembrolizumab; others receive standard local therapy followed by adjuvant pembrolizumab

42 weeks

Cycles 3-9, administered every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing Pembrolizumab in patients after they've undergone tumor removal surgery. Patients will receive two cycles of Pembrolizumab followed by MRI/CT scans and cystoscopy to check response. Those responding well continue on Pembrolizumab; others follow standard care then get 'adjuvant' Pembrolizumab.

How Is the Trial Designed?

Group I: Experimental Group Experimental Treatment 1 Intervention

Cycles 1-2 (Pembrolizumab): 400 mg of Pembrolizumab intravenously (Administered Day 1 of 42 day Cycle) If complete response of treatment is observed then maintenance therapy will be given. All other patients will receive with standard of care local therapy (cystectomy or chemo-radiation) as per their treating physicians followed by "adjuvant" pembrolizumab. Cycle 3-9 (Maintenance or Adjuvant Single agent Pembrolizumab): 400 mg of Pembrolizumab intravenously (Administered Day 1 of 42 day Cycle)

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Vaibhav Patel

Lead Sponsor

Trials

1

Recruited

50+

Matthew Galsky

Lead Sponsor

Trials

12

Recruited

470+

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

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In the PURE-01 study involving 50 patients with muscle-invasive bladder carcinoma, neoadjuvant treatment with pembrolizumab resulted in a pathologic complete response (pT0) in 42% of patients, demonstrating its efficacy as a pre-surgery immunotherapy.

The study found that patients with high PD-L1 expression (CPS ≥ 10%) had a significantly higher rate of pT0 (54.3%) compared to those with lower expression (13.3%), suggesting that pembrolizumab may be particularly effective in patients with PD-L1-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. Necchi, A., Anichini, A., Raggi, D., et al.[2021]

In a study comparing 121 patients treated with pembrolizumab to 67 patients receiving conventional chemotherapy for advanced urothelial carcinoma, pembrolizumab showed a significant improvement in overall survival with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death compared to chemotherapy.

Despite the older age and poorer health status of patients receiving pembrolizumab, the treatment demonstrated a clinical benefit over traditional chemotherapy, suggesting its effectiveness as a second-line therapy in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of pembrolizumab with conventional chemotherapy after first-line platinum-based chemotherapy for advanced urothelial carcinoma in real-world practice: A multicenter retrospective study. Narita, T., Hatakeyama, S., Numakura, K., et al.[2021]

In the PURE-01 study involving 84 patients with muscle-invasive bladder cancer, higher RNA-based immune signature scores were significantly associated with a complete response to pembrolizumab, indicating its potential effectiveness as a neoadjuvant therapy.

Unlike pembrolizumab, the same immune signatures did not predict outcomes for patients receiving standard chemotherapy, suggesting that gene expression profiling could help personalize treatment strategies for better outcomes in bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Molecular Subtyping and Immune Infiltration on Pathological Response and Outcome Following Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer. Necchi, A., Raggi, D., Gallina, A., et al.[2021]

In a study of 39 patients with muscle-invasive bladder cancer, the combination of gemcitabine, cisplatin, and the immune checkpoint inhibitor pembrolizumab was effective, achieving pathologic downstaging in 56% of patients and complete pathologic response in 36%.

The treatment was generally safe, with common side effects including thrombocytopenia, anemia, and neutropenia, but no severe immune-related adverse events were reported, indicating a manageable safety profile for this neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. Rose, TL., Harrison, MR., Deal, AM., et al.[2022]

In a study involving 33 patients with advanced urothelial cancer, pembrolizumab demonstrated anti-tumor activity, with a 26% overall response rate, including 11% complete responses and 15% partial responses, after a median follow-up of 13 months.

The treatment was found to have an acceptable safety profile, with common side effects including fatigue and peripheral edema, and no treatment-related deaths reported, supporting further investigation in larger phase 2 and 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study. Plimack, ER., Bellmunt, J., Gupta, S., et al.[2022]

In a study of 78 patients with advanced urothelial carcinoma treated with pembrolizumab, the median overall survival was 7.3 months, and the estimated survival rate at 6 months was 61.5%, indicating its efficacy in a real-life setting.

The treatment was generally well-tolerated, with the most common side effects being fatigue and gastrointestinal issues, but no severe adverse events occurred in more than 5% of patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study. Dang, E., Vallée, A., Lepage-Seydoux, C., et al.[2022]

In the Phase III KEYNOTE-045 trial, pembrolizumab significantly improved overall survival in patients with second-line metastatic urothelial carcinoma compared to standard treatments like docetaxel, paclitaxel, and vinflunine.

Early results from the Phase II KEYNOTE-052 trial suggest that pembrolizumab is effective for first-line treatment in patients with metastatic urothelial carcinoma who are not eligible for cisplatin, leading to its FDA approval for these indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. Lundgren, KT., Farina, MS., Bellmunt, J.[2018]

Pembrolizumab, an immunotherapy for advanced bladder cancer, led to significant tumor shrinkage after just one injection, demonstrating its efficacy in treating this type of cancer.

The patient experienced immune-related adverse events, specifically myasthenia gravis and myocarditis, which were effectively managed with early corticosteroid treatment, highlighting the importance of monitoring and addressing side effects in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced myasthenia gravis with myositis and presumable myocarditis in a patient with bladder cancer. Todo, M., Kaneko, G., Shirotake, S., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, showed a strong antitumor effect in a 70-year-old female patient with unresectable bladder cancer, but it also led to a grade 3 asthma attack as an immune-related adverse event.

The patient's asthma was linked to changes in immune cell markers, specifically increased CTLA-4 and TIM-3 in CD4+ T cells and a rise in Th17 cells, suggesting that these immune responses could be indicators of both adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of bronchial asthma as an immune-related adverse event of pembrolizumab treatment for bladder cancer: A case report. Hamada, K., Yoshimura, K., Oshinomi, K., et al.[2022]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

Citations

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Pembrolizumab improves outcomes in high-risk bladder ... In preliminary data on overall survival, at three years, about 61% of patients in the pembrolizumab group were still alive, compared with about ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6452591/

Pembrolizumab in the treatment of locally advanced or ... An updated efficacy analysis with all patients having ⩾6 months of follow up demonstrated an ORR of 29% (95 CI, 24–34%) and a CR rate of 7%. The median time to ...

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

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4577

Pembrolizumab (pembro) with chemoradiotherapy (CRT) ... Results: From 2016 – 2021, 28 pts (93% male, median age 72, 96% pure urothelial carcinoma, 29% with carcinoma in situ, 90% pT2) were enrolled at ...

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Merck's KEYTRUDA® (pembrolizumab) Significantly ... “These Phase 3 data mark the first time KEYTRUDA has shown a clinically meaningful improvement in DFS as adjuvant therapy in urothelial carcinoma,” said Dr.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36737362/

The MK-3475-992/KEYNOTE-992 Trial Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Chemoradiotherapy Versus Chemoradiotherapy Alone in Muscle-invasive Bladder ...

7. keytruda.com keytruda.com/advanced-urothelial-bladder-cancer/previously-treated-clinical-trials/

clinical trials - Advanced urothelial bladder cancer Half of the patients on KEYTRUDA were alive without their cancer spreading, growing, or getting worse at 2.1 months, compared to 3.3 months for patients on ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03711032

NCT03711032 | Efficacy and Safety of Pembrolizumab (MK ... Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) ...

9. 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 safety profile of KEYTRUDA plus Padcev in this study was consistent with the known safety profiles of each agent. No new safety signals were ...