37 Participants Needed

Pembrolizumab + BCG for Bladder Cancer

Recruiting at 7 trial locations
GD
DB
GI
Eugene Pietzak, MD - MSK Urologic Surgeon
Overseen ByEugene Pietzak, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out the effectiveness of pembrolizumab in combination with BCG as a first line therapy for participants with high grade T1 bladder cancer who are at "high risk" for BCG alone to be ineffective and are seeking an alternative treatment option to radical cystectomy. There is biologic rationale for combining pembrolizumab and BCG as two distinct immunotherapies with possible additive or synergistic activity in urothelial cancer. The combination of pembrolizumab with BCG will also be evaluated in an exploratory cohort of patients with upper tract urothelial cancer.

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, if you are on medications for active infections, autoimmune diseases, or are receiving live vaccines, you may need to discuss this with the trial team.

What data supports the effectiveness of the drug Pembrolizumab + BCG for bladder cancer?

Pembrolizumab has been approved by the FDA for patients with bladder cancer that does not respond to BCG treatment, showing it can be effective in these cases. Additionally, studies like KEYNOTE-676 are evaluating the combination of pembrolizumab and BCG for persistent high-risk bladder cancer, suggesting potential benefits of this combination.12345

Is the combination of Pembrolizumab and BCG safe for treating bladder cancer?

Research shows that the combination of Pembrolizumab (Keytruda) and BCG has been studied for safety in patients with bladder cancer, particularly those with high-risk, non-muscle invasive bladder cancer. A Phase I trial focused on the safety of this combination, indicating that it is being carefully evaluated for human use.23456

How is the drug Pembrolizumab + BCG unique for treating bladder cancer?

Pembrolizumab + BCG is unique because it combines an immune-boosting vaccine (BCG) with a drug (pembrolizumab) that helps the immune system attack cancer cells by blocking a protein called PD-1, which can make cancer cells invisible to the immune system. This combination is particularly used for patients whose bladder cancer does not respond to BCG alone, offering a new option for those with limited treatment choices.13457

Research Team

GI

Gopakumar Iyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with high-risk T1 bladder cancer or upper tract urothelial carcinoma who haven't had BCG therapy, are not candidates for certain surgeries, and have no evidence of metastasis. They must be able to consent, use birth control if applicable, and meet specific health criteria. Exclusions include recent heart attacks, major surgery within the last month, pregnancy, inability to follow procedures, live vaccines recently taken or needed soon.

Inclusion Criteria

Be willing and able to provide written informed consent/assent for the trial
I have T1 bladder cancer and have not had BCG therapy.
My bladder or urinary tract cancer was confirmed with specific tests at MSK.
See 12 more

Exclusion Criteria

Pregnant (positive pregnancy test) or lactating
Inability to comply with study and/or follow-up procedures
I have previously been treated with specific medications.
See 15 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab (MK-3475) and BCG as first-line treatment for high-risk T1 bladder cancer or high-grade NMI-UTUC

48 weeks
9 visits (in-person) for pembrolizumab infusions, weekly visits for 6 weeks for BCG therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • Bacillus Calmette-Guérin (BCG)
  • Pembrolizumab (MK-3475)
Trial OverviewThe trial is testing pembrolizumab combined with BCG as a first-line treatment for patients with high-grade non-muscle-invasive bladder cancer at 'high risk' where BCG alone may fail. It aims to see if this combination can be an alternative to more invasive treatments like radical cystectomy.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: High Risk T1 Bladder Cancer CohortExperimental Treatment2 Interventions
Pts will receive pembrolizumab/MK-3475 after transurethral resection of bladder tumor/TURBT in comb w/BCG as initial therapy. Pembrolizumab (MK-3475) will be administered as a 400 mg IV infusion at 6-wk intervals for 9 doses over a 48-wk period, unless there is unacceptable toxicity or other reasons to discontinue treatment occur. Intravesical BCG therapy (TICE strain, 50 mg) will be given 1x-weekly for 6 consecutive wks as a standard induction course, followed by maintenance BCG consistent w/standard clinical practice. BCG will start on wk 3 after the first infusion of pembrolizumab (400 mg) to allow for initial priming of T cells to further enhance the effects of BCG treatment.
Group II: Exploratory cohort for high-grade non-muscle-invasive upper tract urothelial carcinomaExperimental Treatment2 Interventions
Pts will receive pembrolizumab (MK-3475) administered after ureteroscopy/laser ablation in comb w/BCG as initial therapy. Pembrolizumab (MK-3475) will be administered as 400 mg IV infusion at 6-week intervals for 9 doses over a 48-week period, unless there is unacceptable toxicity or other reasons that would warrant the discontinuation of treatment. Pts will receive once-weekly BCG therapy (TICE strain, 50 mg) for 6 consecutive wks as a standard induction course administered through a percutaneous nephrostomy tube in antegrade fashion for patients with high-grade NMI-UTUC, consistent with standard clinical practice. BCG will start on wk 3 after the first infusion of pembrolizumab (400 mg) to allow for initial priming of T cells to further enhance the effects of BCG treatment.

Bacillus Calmette-Guérin (BCG) is already approved in United States, Canada, European Union for the following indications:

🇺🇸
Approved in United States as TheraCys for:
  • Non-muscle invasive bladder cancer
  • Upper tract urothelial carcinoma
🇨🇦
Approved in Canada as Immun BCG for:
  • Non-muscle invasive bladder cancer
🇪🇺
Approved in European Union as TICE BCG for:
  • Non-muscle invasive bladder cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

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 profile image

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 involving 101 patients with BCG-unresponsive non-muscle-invasive bladder cancer, pembrolizumab showed a promising clinical complete response rate of 41% at 3 months, indicating its potential as an effective treatment option for patients who cannot undergo surgery.
The treatment was generally well-tolerated, with only 13% of patients experiencing grade 3 or 4 adverse events, suggesting that pembrolizumab is a safe alternative for patients with limited treatment options.
Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study.Balar, AV., Kamat, AM., Kulkarni, GS., et al.[2022]
This study aims to systematically evaluate the efficacy and safety of Bacillus Calmette-Guerin (BCG) treatment for bladder cancer by reviewing high-quality trials from various databases, ensuring a comprehensive analysis.
The findings will provide crucial evidence to determine the effectiveness of BCG in treating bladder cancer, potentially influencing treatment decisions for patients.
Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review.Zhang, ZH., Yin, L., Zhang, LL., et al.[2023]
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.
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC.Wright, KM.[2021]

References

Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. [2022]
Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review. [2023]
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]
KEYNOTE-676: Phase III study of BCG and pembrolizumab for persistent/recurrent high-risk NMIBC. [2020]
Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment. [2022]
Bacillus Calmette-Guerin vaccine and bladder cancer incidence: Scoping literature review and preliminary analysis. [2021]
Impact of prior intravesical bacillus Calmette-Guerin therapy on the effectiveness of pembrolizumab for patients with metastatic urothelial carcinoma. [2022]