Pembrolizumab + Chemotherapy for Bladder Cancer

(KEYNOTE-866 Trial)

Not currently recruiting at 227 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

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

Disqualifiers: Metastatic disease, Immunodeficiency, Transplant, others

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: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of a new treatment, pembrolizumab (an immunotherapy drug), with chemotherapy to determine its effectiveness for people with muscle-invasive bladder cancer. Researchers aim to discover if adding pembrolizumab before and after surgery improves outcomes compared to using only chemotherapy and a placebo. The trial seeks participants with bladder cancer that hasn't spread and who are eligible for surgery to remove the bladder and nearby lymph nodes. Participants must have a mostly urothelial type of bladder cancer and should not have received certain prior treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the combination of pembrolizumab, gemcitabine, and cisplatin is generally safe for patients. In earlier studies, this treatment mix improved outcomes for bladder cancer patients and was well-tolerated. For instance, one study found that while some side effects occurred, they were not severe for most people and could be managed.

Another study found that adding pembrolizumab to gemcitabine and cisplatin was well-tolerated and showed promising results. Patients could handle the treatment without major problems. Overall, the treatment has demonstrated a good safety profile, making it a viable option for patients considering joining a clinical trial for bladder cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Researchers are excited about combining pembrolizumab with chemotherapy and surgery for bladder cancer because it offers a fresh approach to treatment. Unlike the standard care that often focuses solely on chemotherapy and surgery, pembrolizumab is an immunotherapy that works by boosting the body's immune system to better recognize and attack cancer cells. This unique mechanism of action could potentially enhance the effectiveness of chemotherapy drugs like cisplatin and gemcitabine, offering a more powerful one-two punch against the cancer. The hope is that by integrating immunotherapy with traditional treatments, patients might experience improved outcomes and longer-lasting results.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

This trial will compare two treatment approaches for bladder cancer. In one arm, participants will receive pembrolizumab combined with the chemotherapy drugs gemcitabine and cisplatin, followed by surgery. Studies have shown that pembrolizumab with gemcitabine and cisplatin can help treat bladder cancer, with research indicating that this combination helps shrink tumors. Early results have been promising, and patients generally tolerated the treatment well. In the other arm, participants will receive a placebo instead of pembrolizumab, alongside gemcitabine and cisplatin, followed by surgery. These findings suggest that the pembrolizumab combination could be a strong option for bladder cancer patients. ^{1 2 3 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 muscle-invasive bladder cancer who are eligible for cisplatin and surgery. They must have good organ function, agree to use contraception, and have a performance status of 0 or 1. Excluded are those with certain psychiatric disorders, recent live vaccines, other active cancers within the last three years (with exceptions), prior treatments for MIBC or specific immunotherapies, advanced disease stages beyond N1M0, cisplatin ineligibility, recent anticancer therapies or radiotherapy to the bladder.

Inclusion Criteria

My bladder cancer has not spread beyond my pelvis, confirmed by scans.

I am fully active or can carry out light work.

I agree to follow the study's rules for using birth control.

Exclusion Criteria

I cannot receive cisplatin due to specific health reasons.

I have received an organ or tissue transplant from another person.

I have been diagnosed with an immunodeficiency or have HIV, Hepatitis B, or active Hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive 4 preoperative cycles of pembrolizumab or placebo plus gemcitabine and cisplatin

8-12 weeks

4 visits (in-person)

Surgery

Participants undergo surgery following neoadjuvant chemotherapy

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive up to 13 cycles of postoperative pembrolizumab or placebo

Approximately 39 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 72 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine
• Pembrolizumab
• Placebo
• Radical Cystectomy Plus Pelvic Lymph Node Dissection

Trial Overview The study tests if adding pembrolizumab (an immune therapy drug) to standard chemotherapy before and after bladder removal surgery is better than placebo plus chemotherapy. Participants will be randomly assigned to receive either pembrolizumab or a placebo alongside their chemo regimen.

How Is the Trial Designed?

Group I: Pembrolizumab + Gemcitabine + Cisplatin + Surgery Experimental Treatment 4 Interventions

Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.

Group II: Placebo + Gemcitabine + Cisplatin + Surgery Placebo Group 4 Interventions

Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

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

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

Published Research Related to This Trial

In a phase 2 study involving 370 patients with advanced urothelial cancer who were ineligible for cisplatin-based chemotherapy, first-line treatment with pembrolizumab resulted in a 24% objective response rate, with 83% of these responses ongoing at a median follow-up of 5 months.

Pembrolizumab demonstrated acceptable safety, with only 10% of patients experiencing serious treatment-related adverse events, making it a viable treatment option for patients with significant comorbidities or poor prognostic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Balar, AV., Castellano, D., O'Donnell, PH., et al.[2022]

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, a checkpoint inhibitor, has been shown to significantly improve overall survival in patients with locally advanced or metastatic urothelial carcinoma who have progressed after cisplatin-containing chemotherapy, compared to standard chemotherapy options.

Additionally, evidence from Phase 1 and 2 trials suggests that checkpoint inhibitors like pembrolizumab are effective as a first-line treatment for patients who cannot tolerate cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of bladder cancer. Sundahl, N., Rottey, S., De Maeseneer, D., et al.[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]

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]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8560445/

Successful treatment of metastatic bladder cancer by ... We report a successful case in which gemcitabine‐cisplatin re‐challenge after pembrolizumab therapy was effective in metastatic bladder cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02690558

NCT02690558 | Phase 2 Study of Pembrolizumab in ... The purpose of this study is to evaluate whether adding pembrolizumab (Keytruda) to the combination of gemcitabine and cisplatin will improve shrinkage of the ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4509

Long-term outcomes of pembrolizumab (pembro) in ... TMT combined with pembro was well tolerated and continues to show promising early outcomes data. A large phase 3 trial is underway to further explore this ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8478388/

Phase II Study of Gemcitabine and Split-Dose Cisplatin ... Muscle-invasive bladder cancer (MIBC) has poor outcomes despite aggressive treatment with cisplatin-based neoadjuvant chemotherapy followed by radical ...

5. keytrudahcp.com keytrudahcp.com/efficacy/advanced-biliary-tract-cancer-combination-therapy/

KEYNOTE-966 - Clinical Trial Results | HCP The efficacy of KEYTRUDA in combination with gemcitabine/cisplatin chemotherapy was investigated in KEYNOTE-966, a multicenter, randomized, double-blind ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34428076/

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus ... Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe.

7. urotoday.com urotoday.com/conference-highlights/asco-2021/asco-2021-bladder-cancer/130057-asco-2021-pembrolizumab-in-combination-with-gemcitabine-and-concurrent-hypofractionated-radiation-therapy-as-bladder-sparing-treatment-for-muscle-invasive-bladder-cancer-a-multicenter-phase-2-trial.html

ASCO 2021: Pembrolizumab in Combination With ... Pembrolizumab added to hypofractionated radiotherapy and twice weekly gemcitabine was well-tolerated with promising efficacy in this early analysis: 88% rate of ...