V940 Vaccine + Pembrolizumab for Melanoma

Not currently recruiting at 218 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Ocular melanoma, Heart failure, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 56 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new personalized vaccine, intismeran autogene (also known as V940), combined with the cancer drug pembrolizumab, can better prevent melanoma (a type of skin cancer) from returning compared to pembrolizumab alone. People who have had their melanoma surgically removed and have not yet received other treatments may be suitable candidates. Participants will receive either the combination of the new vaccine and pembrolizumab or a placebo with pembrolizumab to determine which is more effective at preventing cancer recurrence. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer prevention.

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 HIV-infected, you must have well-controlled HIV on anti-retroviral therapy (ART).

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

Research has shown that the combination of intismeran autogene (formerly mRNA-4157 or V940) and pembrolizumab is generally safe. Previous studies tested this treatment in individuals with solid tumors, focusing on tolerability without serious side effects.

The combination of V940 and pembrolizumab has shown promising results in other studies. Evidence suggests that this combination can reduce the risk of cancer recurrence by almost half compared to pembrolizumab alone, indicating both effectiveness and good tolerability.

Since pembrolizumab is already approved for other conditions, extensive safety information is available. This ensures that testing the combination with V940 is conducted responsibly. However, it is important to remember that any treatment can have side effects, which may vary among individuals. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Researchers are excited about the V940 vaccine combined with pembrolizumab for treating melanoma because it introduces a novel approach to cancer therapy. Most treatments for melanoma, like traditional immunotherapies, aim to boost the body's immune response to attack cancer cells. However, the V940 vaccine is unique as it customizes the immune response by using a personalized mRNA approach, potentially enhancing the body's ability to recognize and destroy melanoma cells. This combination with pembrolizumab, a well-established immunotherapy, might improve efficacy by offering a dual mechanism of action that could lead to better outcomes for patients.

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

In this trial, participants will receive either the V940 vaccine (also called mRNA-4157) with pembrolizumab or a placebo with pembrolizumab. Research has shown that the V940 vaccine combined with pembrolizumab can significantly aid in treating melanoma, a type of skin cancer. Specifically, studies found that this combination reduced the chance of cancer returning by 49% compared to using pembrolizumab alone. It also lowered the risk of cancer spreading or causing death by 62%. These findings suggest that the V940 vaccine with pembrolizumab is a promising option for preventing melanoma recurrence. ^{1 2 3 4 6}

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 melanoma who have had surgery but no other systemic therapy. Participants must be disease-free post-surgery, not more than 13 weeks from their last resection, and if HIV-positive, well-controlled on ART. It excludes those with ocular/mucosal melanoma, active heart failure within 6 months, prior cancer therapies or vaccines, another recent or active spreadable cancer.

Inclusion Criteria

I am currently free of any signs of my disease.

I have HIV and it is well controlled with medication.

I have only had surgery for my melanoma, no other treatments.

Exclusion Criteria

Has severe reaction to study medications or any of their substance used to prepare a drug

My cancer has spread and cannot be surgically removed.

I am still recovering from major surgery or have ongoing complications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 9 doses of V940 or placebo via IM injection every 3 weeks and pembrolizumab via IV infusion every 6 weeks, for up to approximately 56 weeks or until disease recurrence or unacceptable toxicity

56 weeks

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after treatment

Up to approximately 85 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• V940

Trial Overview The study tests V940 (an individualized neoantigen therapy) combined with pembrolizumab against pembrolizumab alone to see which is better at preventing the return of melanoma after surgical removal. The safety of this combination and its effectiveness in keeping patients cancer-free are being evaluated.

How Is the Trial Designed?

Group I: Intismeran autogene + Pembrolizumab Experimental Treatment 2 Interventions

Participants receive up to 9 doses of intismeran autogene via an intramuscular (IM) injection (every 3 weeks) plus up to 9 doses of pembrolizumab via an intravenous (IV) infusion (once every 6 weeks) until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever is sooner.

Group II: Placebo + Pembrolizumab Active Control 2 Interventions

Participants receive up to 9 doses of dose matched placebo to intismeran autogene via an IM injection (every 3 weeks) plus up to 9 doses of pembrolizumab via an IV infusion (once every 6 weeks) until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever is sooner.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

The KEYNOTE-D36 trial is a phase II study designed to evaluate the safety and effectiveness of the personalized neoepitope vaccine EVX-01 combined with pembrolizumab in patients with unresectable or metastatic melanoma who have not previously received checkpoint inhibitor therapy.

The primary goal of the trial is to determine if EVX-01 can enhance the overall response rate in patients who initially show stable disease or a partial response to pembrolizumab, providing critical data before advancing to larger phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE - D36: personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma. Long, GV., Ferrucci, PF., Khattak, A., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In the KEYNOTE-030 expanded access program, 979 patients with advanced melanoma received pembrolizumab, showing an objective response rate of 14.5%, indicating its efficacy in this difficult-to-treat population.

The treatment was generally well-tolerated, with 19.1% of patients experiencing treatment-related adverse events, but no treatment-related deaths were reported, supporting the safety of pembrolizumab for patients with advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program. Gangadhar, TC., Hwu, WJ., Postow, MA., et al.[2018]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

The phase IIb KEYNOTE-942 trial suggests that the investigational mRNA-4157/V940 vaccine combined with pembrolizumab may significantly reduce the risk of disease recurrence in high-risk melanoma patients after surgery.

Patients receiving this combination therapy showed better outcomes compared to those treated with only the PD-1 inhibitor, indicating a promising new approach for adjuvant therapy in melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA Vaccine Slows Melanoma Recurrence. [2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05933577

NCT05933577 | A Clinical Study of Intismeran Autogene ... Researchers want to know if intismeran autogene with pembrolizumab is better than receiving pembrolizumab alone at preventing the cancer from returning.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38246194/

Individualised neoantigen therapy mRNA-4157 (V940) plus ... Our study aimed to evaluate whether mRNA-4157 (V940), a novel mRNA-based individualised neoantigen therapy, combined with pembrolizumab, improved recurrence- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03897881

NCT03897881 | An Efficacy Study of Adjuvant Treatment ... The purpose of this study is to assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence free survival (RFS)

4. aimatmelanoma.org aimatmelanoma.org/update-on-the-state-of-vaccines-for-melanoma/

Update on the State of Vaccines for Melanoma Data from the three-year trial update reported a 49% risk reduction in recurrence with mRNA-4157 plus pembrolizumab. Adding the mRNA vaccine ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03313778

Study Details | NCT03313778 | Safety, Tolerability, and ... The purpose of this study is to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone and in combination in participants with solid tumors.