Pembrolizumab + BCG for Bladder Cancer

Not currently recruiting at 274 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: BCG

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Metastatic UC, Active autoimmune, others

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: 3

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for individuals with high-risk non-muscle invasive bladder cancer (HR NMIBC), a type of bladder cancer that hasn't spread to the bladder muscle but could worsen or return. Researchers are testing whether adding pembrolizumab (a drug that helps the immune system fight cancer) to BCG (a common bladder cancer treatment) is more effective at preventing cancer from spreading or returning than using BCG alone. The trial also evaluates the safety and tolerability of these treatments for patients. Individuals diagnosed with HR NMIBC, who have undergone surgery to remove visible tumors, and may have cancer that persists or returns after BCG treatment could be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to access potentially effective treatments early.

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 chronic systemic steroid therapy or any other form of immunosuppressive therapy, you must stop these at least 7 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining pembrolizumab and BCG (Bacillus Calmette-Guerin) has been studied for safety in treating bladder cancer. In previous studies, pembrolizumab, a type of immunotherapy, proved effective in similar situations. These studies also monitored any side effects patients might experience.

Pembrolizumab already has FDA approval for other cancers, indicating its well-established safety. When used with BCG for bladder cancer, researchers focus on how well patients tolerate the treatment. Other studies found that while some side effects can occur, many patients manage the treatment quite well.

Treatments can affect people differently. It's important to discuss with your doctor what to expect and whether joining the trial is a good choice for you. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine pembrolizumab, an immune checkpoint inhibitor, with BCG, a standard bladder cancer treatment. Unlike most current therapies that solely rely on BCG to stimulate the immune system, pembrolizumab works by blocking the PD-1 pathway, which cancer cells use to evade immune detection. This dual approach aims to enhance the body's immune response more effectively than BCG alone. Additionally, the trial investigates different dosages and schedules, potentially offering tailored treatment options for various patient needs.

What evidence suggests that this trial's treatments could be effective for high-risk non muscle invasive bladder cancer?

Research shows that adding pembrolizumab to BCG (Bacillus Calmette-Guérin) therapy may enhance treatment for high-risk non-muscle invasive bladder cancer. In this trial, some participants will receive a combination of BCG and pembrolizumab, while others will receive BCG alone. Studies have found that pembrolizumab can help when BCG alone isn't effective and may reduce the likelihood of cancer returning or worsening. One study found that pembrolizumab alone was effective in patients whose bladder cancer did not respond to BCG. Another report indicates that combining BCG and pembrolizumab does not increase urinary side effects. Overall, these findings suggest that adding pembrolizumab to BCG could improve outcomes for patients with this type of bladder cancer. ^{1 3 4 6 7}

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 high-risk non-muscle invasive bladder cancer (HR NMIBC) that's persistent or recurrent after BCG therapy, or who haven't had BCG treatment. Participants need good organ function, must not be pregnant or breastfeeding, and agree to use contraception. Exclusions include active tuberculosis, recent other cancers, HIV infection, certain prior treatments including anti-PD-1/L1/L2 agents, and specific contraindications to BCG.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My bladder cancer returned or persisted after BCG therapy.

I've had surgery to remove bladder tumors.

Exclusion Criteria

I have not had any cancer treatment or experimental drugs in the last 4 weeks.

I have an immune system disorder or have been on steroids or other immune-weakening medicines recently.

Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BCG (Induction and Maintenance) in combination with pembrolizumab administered intravenously

Up to 2 years

Every 3 weeks for 35 doses or every 6 weeks for 9 doses

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• BCG
• Pembrolizumab

Trial Overview The study tests the effectiveness of pembrolizumab combined with BCG against BCG alone in HR NMIBC patients. It aims to see if the drug duo works better for complete response rate in those previously treated with BCG (Cohort A), and event-free survival in new patients (Cohort B).

How Is the Trial Designed?

Group I: BCG plus Pembrolizumab: Post-induction Cohort A (Arm A-1) Experimental Treatment 2 Interventions

Participants receive BCG (Induction and Maintenance) in combination with 200 mg pembrolizumab administered intravenously (IV) every 3 weeks (Q3W) for 35 doses (\~2 years).

Group II: BCG plus Pembrolizumab: BCG Naïve Cohort B-Reduced Maintenance (Arm B-1) Experimental Treatment 2 Interventions

Participants receive BCG (Induction and reduced Maintenance) in combination with 400 mg pembrolizumab administered IV every 6 weeks (Q6W) for 9 doses (\~1 year).

Group III: BCG plus Pembrolizumab: BCG Naïve Cohort B-Full Maintenance (Arm B-2) Experimental Treatment 2 Interventions

Participants receive BCG (Induction and full Maintenance) in combination with 400 mg pembrolizumab administered IV Q6W for 9 doses (\~1 year).

Group IV: BCG Monotherapy: Post-induction Cohort A (Arm A-2) Experimental Treatment 1 Intervention

Participants receive BCG monotherapy (Induction and Maintenance).

Group V: BCG Monotherapy: BCG Naïve Cohort B (Arm B-3) Experimental Treatment 1 Intervention

Participants receive BCG monotherapy (Induction and Maintenance).

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

Approved in United States as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

Approved in European Union as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

Approved in Canada as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

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

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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]

The KEYNOTE-676 study aims to evaluate the safety and efficacy of pembrolizumab combined with Bacillus Calmette-Guérin (BCG) therapy in patients with high-risk nonmuscle-invasive bladder cancer (NMIBC) who have not responded to initial BCG treatment.

This Phase III trial is significant as it addresses the need for effective treatment options for patients with recurrent or BCG-unresponsive NMIBC, a group that currently has limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-676: Phase III study of BCG and pembrolizumab for persistent/recurrent high-risk NMIBC. Kamat, AM., Shore, N., Hahn, N., et al.[2020]

The combination of intravesical Bacillus Calmette-Guérin (BCG) and systemic pembrolizumab was found to be safe in a phase I trial involving 18 patients with high-grade non-muscle-invasive bladder cancer, with 69% of treated patients showing no evidence of disease after 3 months.

Despite some treatment-related adverse events, including one severe case of adrenal insufficiency and several grade 3 adverse events, the overall safety profile supports further investigation, leading to the initiation of a phase III trial to evaluate the efficacy of this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Alanee, S., Sana, S., El-Zawahry, A., et al.[2022]

In a study of 755 patients with metastatic, chemo-resistant urothelial carcinoma treated with pembrolizumab, a history of non-muscle invasive bladder cancer (NMIBC) treatment, including BCG therapy, did not significantly impact overall survival or treatment response outcomes.

Patients with a history of BCG treatment had a lower objective response rate compared to those without an NMIBC history, but overall disease control rates were similar, indicating that prior NMIBC treatment does not adversely affect the efficacy of pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prior intravesical bacillus Calmette-Guerin therapy on the effectiveness of pembrolizumab for patients with metastatic urothelial carcinoma. Taoka, R., Kobayashi, T., Hidaka, Y., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review. Zhang, ZH., Yin, L., Zhang, LL., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32162533/

KEYNOTE-676: Phase III study of BCG and pembrolizumab ... Aberrant programmed death 1 signaling has been implicated in BCG resistance and bladder cancer recurrence and progression, and pembrolizumab has shown efficacy ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1558767325001454

A Systematic Review and Meta-Analysis of the ... Pembrolizumab monotherapy showed antitumor activity and manageable toxicity in patients with BCG-unresponsive high-risk Ta or T1 bladder cancer ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38554570/

Urinary bother, Urinalysis, and Two-Year Efficacy Follow- ... Conclusions: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response ...

4. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-471942

New Treatment Options for Non–Muscle-Invasive Bladder ... Despite the effectiveness of Bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT), BCG fails nearly 40 ...

5. keytrudahcp.com keytrudahcp.com/efficacy/nmibc/

KEYNOTE-057 - Clinical Trial Results | HCP Median follow-upc for the 96 patients treated with KEYTRUDA was 58.0 months (range: 4.6–72.5 months). 23.1% (9/39) of the responding patients maintained a CR ...

6. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2019-0817

KEYNOTE-676: Phase III study of BCG and pembrolizumab ... Phase III KEYNOTE-676 study, which will evaluate the efficacy and safety of pembrolizumab in combination with BCG in patients with persistent/recurrent high- ...

7. 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) ...