Pembrolizumab + V940 for Bladder Cancer

Recruiting at 105 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Pembrolizumab

Must not be taking: Live vaccines

Disqualifiers: Active infection, Pneumonitis, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for high-risk muscle-invasive urothelial carcinoma, a type of bladder cancer. Researchers aim to determine if a combination of pembrolizumab (an immunotherapy) and V940 (also known as intismeran autogene, a personalized mRNA treatment) can prevent cancer recurrence after surgery. They compare this combination to pembrolizumab with a placebo to assess effectiveness and safety. Individuals who have undergone surgery for bladder cancer and face a high risk of recurrence might be suitable for this study. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

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, it does mention that participants should not have received certain cancer treatments before joining the trial.

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

Previous studies have generally found pembrolizumab to be well-tolerated by patients. As a type of immunotherapy, it helps the body's immune system fight cancer. Common side effects include fatigue, itching, and rash, while more serious side effects are less common but possible.

Research suggests that intismeran autogene, also known as V940, may be safe when combined with pembrolizumab. Studies indicate that this combination can reduce the risk of cancer returning or spreading. V940 might cause flu-like symptoms, such as fever and chills, but serious side effects are infrequently reported.

For enfortumab vedotin (EV), used with other treatments in one part of the trial, studies have found it to be mostly well-tolerated. It can cause side effects like skin rash and tiredness. Occasionally, more serious side effects may occur, but they are rare.

Overall, these treatments have been studied and are considered to have manageable side effects for most patients. However, discussing potential risks and benefits with a healthcare provider is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and V940 (intismeran autogene) for bladder cancer because it offers a unique approach compared to traditional treatments like chemotherapy and surgery. Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells, while V940 is a personalized cancer vaccine designed to boost this immune response further. This combination aims to enhance the body's natural defenses against cancer more effectively than existing therapies. Additionally, the use of V940 as a personalized treatment is a promising innovation, potentially leading to more targeted and effective cancer care.

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

Research has shown that pembrolizumab, a type of immunotherapy, helps the body's immune system find and fight cancer cells. In this trial, some participants will receive pembrolizumab with intismeran autogene (also called V940), which trains the immune system to recognize and destroy cancer cells by identifying specific proteins. Early studies suggest this combination can help people with high-risk muscle-invasive urothelial carcinoma, a type of bladder cancer, live longer without the cancer returning. Another treatment arm in this trial includes enfortumab vedotin (EV), which targets cancer cells to deliver strong medicine directly to them. These treatments are being tested to determine if they can prevent cancer from returning after surgery by strengthening the body's natural defenses. ^{2 3 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 individuals with high-risk muscle-invasive bladder cancer who've had surgery to remove it. Participants must be able to provide blood samples, have their tumor DNA tested, and give a tissue sample for genetic sequencing. They should also be relatively active and mobile (ECOG status 0-2).

Inclusion Criteria

I have been diagnosed with muscle-invasive bladder cancer.

My cancer is mainly urothelial carcinoma.

My cancer is still at high risk after surgery to remove it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive up to 4 cycles of pembrolizumab plus EV and 1 to 4 doses of V940, followed by radical cystectomy and pelvic lymph node dissection

Up to 18 weeks

Adjuvant Treatment

Participants receive up to 13 cycles of pembrolizumab plus up to 5 cycles of EV and 5 to 8 doses of V940

Up to 16 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 28 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• V940

Trial Overview The study is testing the effectiveness of a vaccine called V940 when given with Pembrolizumab versus Pembrolizumab alone in preventing cancer return after surgery. The goal is to see if adding V940 improves disease-free survival.

How Is the Trial Designed?

Group I: Perioperative Cohort: Pembrolizumab + Intismeran autogene + EV and Surgery Experimental Treatment 4 Interventions

Participants will receive neoadjuvant treatment with up to 4 cycles of pembrolizumab plus EV and 1 to 4 doses of intismeran autogene, followed by radical cystectomy \[RC\] plus pelvic lymph node dissection \[PLND\], and then adjuvant treatment with up to 13 cycles of pembrolizumab plus up to 5 cycles of EV and 5 to 8 doses of intismeran autogene (for a total of 9 neoadjuvant plus adjuvant Intismeran autogene doses), or until any of the protocol-specified criteria for discontinuation of study intervention are met. The total duration of treatment is up to approximately 16 months.

Group II: Adjuvant Cohort: Pembrolizumab + Intismeran autogene Experimental Treatment 2 Interventions

Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of intismeran autogene. Intismeran autogene doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.

Group III: Adjuvant Cohort: Pembrolizumab + Placebo Active Control 2 Interventions

Adjuvant Cohort participants receive adjuvant treatment with up to 9 cycles of pembrolizumab plus up to a total of 9 doses of placebo. Placebo doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.

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

ModernaTX, Inc.

Industry Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

Published Research Related to This Trial

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]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, showed a strong antitumor effect in a 70-year-old female patient with unresectable bladder cancer, but it also led to a grade 3 asthma attack as an immune-related adverse event.

The patient's asthma was linked to changes in immune cell markers, specifically increased CTLA-4 and TIM-3 in CD4+ T cells and a rise in Th17 cells, suggesting that these immune responses could be indicators of both adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of bronchial asthma as an immune-related adverse event of pembrolizumab treatment for bladder cancer: A case report. Hamada, K., Yoshimura, K., Oshinomi, K., et al.[2022]

In a study of 78 patients with advanced urothelial carcinoma treated with pembrolizumab, the median overall survival was 7.3 months, and the estimated survival rate at 6 months was 61.5%, indicating its efficacy in a real-life setting.

The treatment was generally well-tolerated, with the most common side effects being fatigue and gastrointestinal issues, but no severe adverse events occurred in more than 5% of patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study. Dang, E., Vallée, A., Lepage-Seydoux, C., 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 (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]

In a study of 370 patients with advanced urothelial carcinoma who were not eligible for cisplatin treatment, first-line pembrolizumab showed an objective response rate of 28.6%, with a median duration of response lasting over 30 months for many patients.

Patients with high PD-L1 expression (CPS ≥ 10) had a significantly better response rate of 47.3% and a median overall survival of 18.5 months, indicating that pembrolizumab is particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer. Vuky, J., Balar, AV., Castellano, D., et al.[2022]

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 1 safety study involving six patients with non-muscle-invasive bladder cancer (NMIBC), intravesical administration of pembrolizumab was well tolerated, with no dose-limiting toxicities observed during dose escalation.

The treatment resulted in low-grade adverse events such as dysuria and fatigue, and importantly, there was no evidence of systemic absorption or immune effects, suggesting a localized action of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer. Woodcock, VK., Chen, JL., Purshouse, K., et al.[2023]

In the KEYNOTE-045 study involving 542 patients with advanced urothelial cancer, pembrolizumab significantly prolonged overall survival compared to standard chemotherapy, demonstrating its efficacy as a treatment option.

Patients receiving pembrolizumab experienced a longer time to deterioration in health-related quality of life (3.5 months) compared to those on chemotherapy (2.3 months), indicating that pembrolizumab not only improves survival but also maintains or enhances quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer. Vaughn, DJ., Bellmunt, J., Fradet, Y., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06305767

NCT06305767 | A Clinical Study of Intismeran Autogene ... The goals of this study are to learn if people who receive intismeran autogene and pembrolizumab are alive and cancer free longer than those who receive ...

2. trialx.com trialx.com/clinical-trials/listings/287778/a-clinical-study-of-v940-treatment-and-pembrolizumab-in-people-with-bladder-cancer-v940-005interpath-005/?&radius=10&place=Seoul,%20etc.&user_country=Korea,%20Republic%20of

A Clinical Study of Intismeran Autogene (V940) Treatment ... Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Enfortumab vedotin (EV) is an antibody drug ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/intismeran-autogene?pn=1

Clinical Trials Using Intismeran Autogene - NCI A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005). Status: Active. Location: 8 ...

4. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06305767/

A Study of Pembrolizumab Plus V940 in Participants With ... The goals of this study are to learn if people who receive intismeran autogene and pembrolizumab are alive and cancer free longer than those who receive ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05933577

A Clinical Study of Intismeran Autogene (V940) Plus ... V940-001 is a Phase 3 global, randomized, double-blind, placebo- and active-comparator-controlled study designed to evaluate the safety and efficacy of V940 ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06305767

NCT06305767 | A Clinical Study of Intismeran Autogene ... The goals of this study are to learn if people who receive intismeran autogene and pembrolizumab are alive and cancer free longer than those who receive placebo ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06833073

A Clinical Study of Intismeran Autogene (V940) and BCG in ... How many people who receive intismeran autogene without BCG have their cancer go away. Official Title. A Phase 2 Open-label Randomized Study of V940 in ...

8. merck.com merck.com/news/moderna-merck-announce-3-year-data-for-mrna-4157-v940-in-combination-with-keytruda-pembrolizumab-demonstrated-sustained-improvement-in-recurrence-free-survival-distant-metastasis-free-su/

Moderna & Merck Announce 3-Year Data For mRNA-4157 ... mRNA-4157 (V940) in combination with KEYTRUDA reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death by 62% compared to ...