Pembrolizumab for Bladder Cancer

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

46 Participants Needed

Trial Summary

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.

What data supports the idea that Pembrolizumab for Bladder Cancer is an effective drug?

The available research shows that Pembrolizumab is effective for treating bladder cancer in several ways. It was approved by the FDA for patients with a specific type of bladder cancer that doesn't respond to other treatments and who can't or don't want to have surgery. In studies, Pembrolizumab was used before surgery for muscle-invasive bladder cancer and showed positive results. It was also compared to traditional chemotherapy for advanced bladder cancer and was found to help patients live longer. This makes it a strong option for those who can't use standard chemotherapy. ^{1 2 3 4 5}

What data supports the effectiveness of the drug pembrolizumab for bladder cancer?

Pembrolizumab has been approved by the FDA for certain types of bladder cancer, showing effectiveness in patients who cannot undergo surgery or have not responded to other treatments. It has also shown benefits in improving survival for advanced bladder cancer patients compared to traditional chemotherapy. ^{1 2 3 4 5}

What safety data is available for pembrolizumab in bladder cancer treatment?

Pembrolizumab, also known as Keytruda or MK-3475, has been evaluated for safety in several studies. It is approved by the FDA for BCG-unresponsive, high-risk, non-muscle invasive bladder cancer. Safety concerns include immune-related adverse events, as reported in a case of pembrolizumab-induced myasthenia gravis with myositis and presumable myocarditis in a bladder cancer patient. The KEYNOTE-012 study assessed its safety in locally advanced or metastatic urothelial cancer, and a real-life study evaluated its safety in metastatic urothelial carcinoma patients. Overall, pembrolizumab has shown clinical benefits but also potential safety risks that need to be monitored. ^{2 6 7 8 9}

Is pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been studied for safety in various conditions, including bladder cancer. Some patients have experienced immune-related side effects, such as myasthenia gravis (a condition causing muscle weakness) and myocarditis (inflammation of the heart). However, it has been approved by the FDA for certain types of bladder cancer, indicating that its benefits may outweigh the risks for some patients. ^{2 6 7 8 9}

Is the drug Pembrolizumab a promising treatment for bladder cancer?

Yes, Pembrolizumab is a promising drug for bladder cancer. It has been approved by the FDA for certain types of bladder cancer that don't respond to other treatments. It has shown to improve survival in advanced bladder cancer and is effective for patients who can't use other common treatments. ^{2 3 8 10 11}

What makes the drug pembrolizumab unique for treating bladder cancer?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets PD-1, helping the immune system attack cancer cells. It is approved for patients with bladder cancer who cannot undergo surgery or have not responded to other treatments, offering a new option for those with limited choices. ^{2 3 8 10 11}

What is the purpose of this trial?

Subjects with cT2-T3N0M0 urothelial cancer of the bladder will be enrolled. After completing two cycles of pembrolizumab, subjects will undergo a restaging MRI of the abdomen and pelvis with a standard acquisition protocol (as outlined in the protocol) as well as CT chest. A CT of the abdomen and pelvis may be performed if there are contraindications to MRI. Patients will also undergo a restaging cystoscopy and biopsies/TURBT as outlined in the protocol. Patients achieving a clinical complete response to treatment (defined in the protocol) will proceed with "maintenance" single agent pembrolizumab followed by surveillance. All other patients will proceed with standard of care local therapy as per their treating physicians followed by "adjuvant" pembrolizumab.

Research Team

Matthew Galsky, M.D.

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 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 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 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]

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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. [2018]

4. United States 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. [2021]

5. Australia 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. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced myasthenia gravis with myositis and presumable myocarditis in a patient with bladder cancer. [2022]

7. England 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. [2022]

8. Switzerland 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. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

11. United States 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. [2022]