Pembrolizumab + BCG for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Gopakumar Iyer, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

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

Disqualifiers: Muscle invasive cancer, Heart failure, Stroke, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

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. ^{1 2 3 4 5}

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. ^{2 3 4 5 6}

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. ^{1 3 4 5 7}

Research Team

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.

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.

Trial 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) (Cancer Vaccine)
• Pembrolizumab (MK-3475) (Monoclonal Antibodies)

Trial Overview The 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

Group I: High Risk T1 Bladder Cancer Cohort Experimental Treatment 2 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 carcinoma Experimental Treatment 2 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

Research Locations Nearby Select from list below to view details:

Memoral Sloan Kettering Basking Ridge (All Protocol Activities) Basking Ridge, NJ

Memorial Sloan Kettering Basking Ridge (All Protocol Activities) Basking Ridge, NJ

Memorial Sloan Kettering Monmouth (All Protocol Activities) Middletown, NJ

Memorial Sloan Kettering Cancer Center (All Protocol Activities) New York, NY

More Trial Locations

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1998

Patients Recruited

602,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4096

Patients Recruited

5,232,000+

References

1. England 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. [2022] Standard treatment for high-risk non-muscle-invasive bladder cancer is transurethral resection of bladder tumour followed by intravesical BCG immunotherapy. However, despite high initial responses rates, up to 50% of patients have recurrence or become BCG-unresponsive. PD-1 pathway activation is implicated in BCG resistance. In the KEYNOTE-057 study, we evaluated pembrolizumab, a PD-1 inhibitor, in BCG-unresponsive non-muscle-invasive bladder cancer.

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

Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review. [2023] This study will systematically assess the efficacy and safety of Bacillus Calmette-Guerin (BCG) for patients with bladder cancer (BC).

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. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-676: Phase III study of BCG and pembrolizumab for persistent/recurrent high-risk NMIBC. [2020] Background: Nonmuscle-invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with high rates of disease recurrence and progression. Current treatment for high-risk NMIBC involves Bacillus Calmette-Guérin (BCG) therapy, but treatment options are limited for patients with recurrent or BCG-unresponsive disease. Aberrant programmed death 1 signaling has been implicated in BCG resistance and bladder cancer recurrence and progression, and pembrolizumab has shown efficacy in patients with BCG-unresponsive high-risk NMIBC. Aim: To describe the rationale and design for the randomized, comparator-controlled Phase III KEYNOTE-676 study, which will evaluate the efficacy and safety of pembrolizumab in combination with BCG in patients with persistent/recurrent high-risk NMIBC after BCG induction therapy. Trial registration number: NCT03711032.

5. Germany 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. [2022] We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment.

6. Italy pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guerin vaccine and bladder cancer incidence: Scoping literature review and preliminary analysis. [2021] The Bacillus Calmette-Guerin (BCG) vaccine has long been used for the prevention of tuberculosis (TB) around the world. BCG is also used as an immunotherapy agent for the treatment of non-muscle invasive urinary bladder cancer. This scoping literature review and preliminary data analysis aims to summarize the literature correlating infantile BCG vaccination with the incidence of future bladder cancer.

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

Impact of prior intravesical bacillus Calmette-Guerin therapy on the effectiveness of pembrolizumab for patients with metastatic urothelial carcinoma. [2022] The aim of this study was to determine whether a history of treatment for non-muscle invasive bladder cancer (NMIBC), including intravesical bacillus Calmette-Guerin (BCG) therapy, affects the treatment outcomes of pembrolizumab in patients with metastatic, chemo-resistant urothelial carcinoma (UC).