Pembrolizumab Combinations for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+27 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Merck Sharp & Dohme Corp.

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

In this study, participants with high risk non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette Guerin (BCG) therapy and who are considered ineligible for or have refused to undergo radical cystectomy, will receive pembrolizumab therapy or pembrolizumab in combination with other investigational agents. The primary study hypothesis is that treatment with pembrolizumab will result in a clinically meaningful response.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot have received chemotherapy, targeted therapy, or radiation therapy within 2 weeks before starting the study treatment, and you must not have received intravesical chemotherapy or immunotherapy after your most recent cystoscopy or TURBT.

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

The available research shows that pembrolizumab is effective for treating bladder cancer in several ways. It has been 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. Studies also show that when combined with other drugs like gemcitabine and cisplatin, pembrolizumab can be used before surgery to help treat muscle-invasive bladder cancer. Additionally, pembrolizumab has been found to be beneficial as a second-line treatment for advanced bladder cancer, especially after initial chemotherapy. This suggests that pembrolizumab can be a valuable option for patients with different stages and types of bladder cancer.

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

Safety data for pembrolizumab in bladder cancer treatment includes its approval by the FDA for BCG-unresponsive, high-risk, non-muscle invasive bladder cancer, indicating an acceptable safety profile. Studies have evaluated immune-related adverse events (irAEs) in patients with advanced urothelial carcinoma treated with pembrolizumab, showing a relationship between irAEs and clinical outcomes. Research on older patients with chemoresistant urothelial carcinoma assessed the safety of pembrolizumab using real-world data. Additionally, pembrolizumab combined with lenvatinib demonstrated acceptable safety in patients with platinum-refractory urothelial carcinoma. Lastly, pembrolizumab was studied as neoadjuvant therapy before radical cystectomy in muscle-invasive bladder carcinoma, further contributing to its safety data.

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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 benefits in improving survival rates in advanced bladder cancer and is effective for patients who can't use standard chemotherapy. It is also being tested in combination with other treatments to enhance its effectiveness.

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Eligibility Criteria

This trial is for adults with high-risk bladder cancer that hasn't spread into the muscle, who didn't respond to BCG therapy and can't or won't have their bladder removed. They need good organ function, no recent other treatments or active infections, and must agree to use contraception.

Inclusion Criteria

My cancer was completely removed surgically.

I cannot or will not undergo major bladder surgery.

I am a woman who can have children, not pregnant, and willing to use birth control.

Exclusion Criteria

I have received a transplant from another person.

I have no progressing cancer except skin cancer or treated in situ cervical or prostate cancer.

I have been treated with drugs targeting immune checkpoints.

Participant Groups

The study tests pembrolizumab alone or combined with other investigational drugs in patients whose bladder cancer remains after BCG treatment. The goal is to see if these therapies can effectively treat the cancer without surgery.

Group I: Pembrolizumab coformulation Experimental Treatment 2 Interventions

Participants with CIS with or without papillary tumors (Cohort C) will receive either pembrolizumab/vibostolimab or favezelimab/pembrolizumab coformulation intravenously Q3W for up to 24 months

Group II: Pembrolizumab Experimental Treatment 1 Intervention

Participants with carcinoma-in-situ (CIS) with or without papillary tumors (Cohort A) and participants with papillary tumors only, without CIS (Cohort B) will receive pembrolizumab, 200 mg, intravenously, every 3 weeks (Q3W) for up to 24 months.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Call for Information (Investigational Site 0076) Syracuse, NY

Call for Information (Investigational Site 0009) Cleveland, OH

Call for Information (Investigational Site 0074) Bala-Cynwyd, PA

Call for Information (Investigational Site 0021) Orange, CA

More Trial Locations

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp. Lead Sponsor

Merck Sharp & Dohme LLC Lead Sponsor

References

1. 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] To assess the clinical benefit of pembrolizumab as second-line therapy for advanced urothelial carcinoma.

2. Germany pubmed.ncbi.nlm.nih.gov

Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma. [2023] The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear.

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

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021] The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.

4. 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] To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer.

5. 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] To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used.

6. New Zealand pubmed.ncbi.nlm.nih.gov

Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab. [2022] To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab.

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab for older patients with chemoresistant urothelial carcinoma assessed using propensity score matching. [2022] We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC).

8. Switzerland pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. [2023] Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. [2018] Pembrolizumab is a humanized monoclonal antibody that targets PD-1. In the Phase III trial KEYNOTE-045, pembrolizumab was associated with a significant overall survival benefit when compared with docetaxel, paclitaxel and vinflunine in second line metastatic urothelial carcinoma (UC). Additionally, in the first line, early results from an interim analysis of the Phase II trial Keynote-052 study indicated that pembrolizumab is efficacious for cisplatin-ineligible patients. Based on data from these trials, pembrolizumab was the most recent among the five checkpoint inhibitors tested in UC to be approved by the US FDA in May 2017. It was granted regular approval for patients with advanced-stage UC who progress after receiving platinum-based chemotherapy and accelerated approval in the first line for patients who are ineligible to receive cisplatin.

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] A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.