Pembrolizumab + Chemoradiotherapy for Bladder Cancer

Recruiting at 185 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids, Anti-PD-1, others

Disqualifiers: Carcinoma, Radiation, Autoimmune, Infection, 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: Unknown

Duration: 24 months

520 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for muscle-invasive bladder cancer (MIBC), a type of cancer confined to the bladder muscles. The study aims to determine if adding pembrolizumab—an immunotherapy that enhances the immune system's ability to fight cancer—to standard chemoradiotherapy (CRT) can extend the time patients live without their cancer worsening. Participants will receive either pembrolizumab with CRT or a placebo with CRT to compare outcomes. This trial is suitable for individuals diagnosed with MIBC who have not experienced cancer spread beyond the bladder and are planning to undergo CRT. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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 immunosuppressive therapy or have received certain treatments like live vaccines recently, you may need to discuss this with the trial team.

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

Research shows that pembrolizumab, a type of immunotherapy, is usually well-tolerated by patients. Studies have found it can help people with advanced cancers, like bladder cancer, live longer. For instance, one study found that about 61% of patients with high-risk bladder cancer were still alive three years after receiving pembrolizumab. Compared to some other cancer treatments, pembrolizumab tends to cause fewer unwanted side effects.

When combined with chemoradiotherapy (a combination of chemotherapy and radiation), the safety results are encouraging. However, chemoradiotherapy can cause side effects, such as nausea or tiredness, but these are usually manageable.

In this phase of the study, researchers are closely examining how well people handle the combination of pembrolizumab with chemoradiotherapy. The advanced stage of the study indicates strong evidence of safety, but ongoing research will provide more detailed information. ^{1 2 3 4 5}

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

Researchers are excited about pembrolizumab for bladder cancer because it offers a fresh approach compared to the traditional treatments like chemotherapy and radiotherapy alone. Pembrolizumab is an immunotherapy that works by unleashing the immune system to attack cancer cells, specifically targeting the PD-1/PD-L1 pathway, which is different from how chemotherapy targets rapidly dividing cells. This combination of pembrolizumab with chemoradiotherapy could enhance the overall effectiveness, potentially leading to better outcomes for patients. Moreover, by integrating pembrolizumab, there's hope for fewer side effects and more durable responses compared to conventional treatments.

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

In this trial, participants will receive either pembrolizumab or a placebo alongside chemotherapy and radiotherapy. Research has shown that pembrolizumab can improve survival rates for people with high-risk bladder cancer. In one study, about 61% of patients who received pembrolizumab were still alive after three years, compared to those who did not receive it. Pembrolizumab helps the immune system find and attack cancer cells. For patients with muscle-invasive bladder cancer, pembrolizumab has been associated with longer survival and better disease control. Early evidence suggests it can significantly impact managing this type of cancer. ^{2 4 6 7 8}

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 set to receive chemoradiotherapy and meet certain health criteria, including good organ function and performance status. Women must not be pregnant or breastfeeding and follow specific contraceptive guidelines; men must agree to use contraception or abstain from heterosexual intercourse.

Inclusion Criteria

My organs are functioning well.

My bladder cancer was confirmed to be invasive and mainly urothelial.

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

Exclusion Criteria

Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

I have an autoimmune disease treated with medication in the last 2 years.

You have a severe allergy to the specific treatments or any of their ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or placebo in combination with chemoradiotherapy (CRT)

24 months

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 95 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Conventional Radiotherapy (Bladder and pelvic nodes)
• Conventional Radiotherapy (Bladder only)
• Fluorouracil (5-FU)
• Hypofractionated Radiotherapy (Bladder only)
• Mitomycin C (MMC)
• Pembrolizumab

Trial Overview The study tests the effectiveness of pembrolizumab (a type of immunotherapy) combined with chemoradiotherapy versus just chemoradiotherapy in treating bladder cancer. The goal is to see if adding pembrolizumab improves survival without the cancer spreading or worsening.

How Is the Trial Designed?

Group I: Pembrolizumab + Chemotherapy + Radiotherapy Experimental Treatment 8 Interventions

Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.

Group II: Placebo + Chemotherapy + Radiotherapy Placebo Group 8 Interventions

Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.

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 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

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]

In the Phase III KEYNOTE-045 trial, pembrolizumab significantly improved overall survival in patients with second-line metastatic urothelial carcinoma compared to standard treatments like docetaxel, paclitaxel, and vinflunine.

Early results from the Phase II KEYNOTE-052 trial suggest that pembrolizumab is effective for first-line treatment in patients with metastatic urothelial carcinoma who are not eligible for cisplatin, leading to its FDA approval for these indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. Lundgren, KT., Farina, MS., Bellmunt, J.[2018]

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 phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

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]

In a study of 38 patients with invasive bladder cancer, concurrent radiotherapy and panitumumab after chemotherapy resulted in a low rate of severe toxicity (16%), comparable to historical rates for cisplatin and radiotherapy.

The treatment achieved a high complete remission rate of 94%, with promising bladder preservation outcomes, suggesting that this approach could be a viable alternative for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. Fransen van de Putte, EE., Pos, F., Doodeman, B., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39282902/

Adjuvant Pembrolizumab versus Observation in Muscle ... Conclusions: Among patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, disease-free survival was significantly ...

2. cancer.gov cancer.gov/news-events/press-releases/2024/high-risk-bladder-cancer-pembrolizumab

Pembrolizumab improves outcomes in high-risk bladder ... In preliminary data on overall survival, at three years, about 61% of patients in the pembrolizumab group were still alive, compared with about ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1613683

Pembrolizumab as Second-Line Therapy for Advanced ... Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events ...

4. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-disease-free-survival-dfs-as-adjuvant-therapy-versus-observation-in-high-risk-patients-with-localized-muscle-invasive-and-locall/

Merck's KEYTRUDA® (pembrolizumab) Significantly ... After a median follow-up of 36.9 months, median OS was 50.9 months (95% CI, 43.8-NE) for KEYTRUDA versus 55.8 months (95% CI, 53.3-NE) for observation. “Even ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0923753422047603

results from KEYNOTE-045 and KEYNOTE-052 after up to ... The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36494006/

Efficacy and safety of pembrolizumab in metastatic ... The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab ...

7. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35601

Efficacy and safety of pembrolizumab in patients with ... Frontline pembrolizumab monotherapy exhibited clinically meaningful and generally consistent efficacy and safety in patients with advanced ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6452591/

Pembrolizumab in the treatment of locally advanced or ... With additional follow up, the survival benefit for pembrolizumab over chemotherapy was further improved with a HR of 0.70 (95% CI 0.57–0.85) at a median follow ...