V940 + Pembrolizumab for Skin Cancer

Recruiting at 37 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Immunotherapy

Must not be taking: Anticancer therapy, Live vaccines

Disqualifiers: Heart failure, Ocular melanoma, others

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

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: Up to 2 years

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if V940 (an experimental treatment) combined with pembrolizumab can effectively stop advanced melanoma from growing or spreading. Advanced melanoma is a serious type of skin cancer that has spread and cannot be removed by surgery. The study compares this new combination treatment to a placebo (a harmless, inactive substance) with pembrolizumab to assess whether patients live longer without the cancer worsening. Individuals with advanced melanoma who have not received prior treatment, except under specific conditions, might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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, certain treatments like recent blood transfusions, specific cancer therapies, or live vaccines may affect eligibility. It's best to discuss your current medications with the trial team.

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

A previous study found that most participants taking the combination of V940 and pembrolizumab experienced mild side effects, classified as grade 1 or 2. However, about 25% of patients encountered more serious side effects, classified as grade 3 or higher. While many tolerated the treatment well, some experienced significant adverse effects. Pembrolizumab is already used to treat advanced melanoma, and its safety profile is well-known. V940, when combined with pembrolizumab, has shown promise but carries some risk of more severe side effects. Patients should always discuss any safety and side effect concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Researchers are excited about V940 combined with pembrolizumab for skin cancer because it introduces a novel approach to treatment. Unlike the standard therapies, which typically focus solely on immune checkpoint inhibitors like pembrolizumab, V940 adds an innovative vaccine component. This vaccine is designed to boost the immune system's ability to recognize and attack cancer cells more effectively. By combining this with pembrolizumab, which helps unleash the body's immune response, there's potential for a more robust attack on skin cancer cells, possibly improving patient outcomes.

What evidence suggests that V940 with pembrolizumab could be an effective treatment for advanced melanoma?

Research has shown that using V940 with pembrolizumab might effectively treat advanced melanoma. In this trial, one group of participants will receive both V940 and pembrolizumab. Studies have found that patients receiving both treatments had a 49% lower chance of cancer recurrence or death compared to those who only received pembrolizumab. Additionally, the likelihood of cancer spreading or causing death was reduced by 62%. This suggests that adding V940 to pembrolizumab could control melanoma more effectively than using pembrolizumab alone. The combination has shown promise in stopping the cancer from growing or spreading. ^{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 adults with advanced melanoma that has spread and can't be removed by surgery. Participants must not have been treated for melanoma, except certain therapies if no relapse occurred within a year after stopping them. They should have at least one measurable tumor and provide tissue samples. People with well-controlled HIV on therapy or past hepatitis C are eligible; those with active hepatitis B can join if they're on antiviral treatment.

Inclusion Criteria

Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

My melanoma is at stage III or IV and cannot be removed with surgery.

I have HIV and it is well controlled with medication.

Exclusion Criteria

I have had treatment for melanoma before, but there may be exceptions.

I haven't received blood products or colony-stimulating factors in the last 2 weeks.

I am HIV-positive with a history of Kaposi's sarcoma or Multicentric Castleman's Disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive V940 or placebo via IM injection every 3 weeks for up to 9 doses (approximately 27 weeks) and pembrolizumab via IV infusion every 6 weeks for up to 17 doses, or until disease progression or discontinuation

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• V940

Trial Overview The study tests whether V940 combined with pembrolizumab extends the time patients live without their melanoma growing compared to placebo plus pembrolizumab. Pembrolizumab is an existing immunotherapy, while V940 is new and aims to boost the immune system's ability to fight cancer.

How Is the Trial Designed?

Group I: V940 + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive 1 mg of V940 via intramuscular (IM) injection every 3 weeks (q3w) for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via intravenous (IV) infusion every 6 weeks (q6w) for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.

Group II: Placebo + Pembrolizumab Active Control 2 Interventions

Participants will receive placebo via IM injection q3w for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via IV infusion q6w for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.

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

Citations

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

Individualised neoantigen therapy mRNA-4157 (V940) plus ... Most treatment-related adverse events were grade 1-2. Grade ≥3 treatment-related adverse events occurred in 25% of patients in the combination ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA9512

3-year update from the mRNA-4157-P201 (KEYNOTE-942) ... RFS benefit in the combo vs pembro arm was maintained with 49% risk reduction in recurrence and/or death (HR [95% CI], 0.510 [0.288–0.906]; 2- ...

3. 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 ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)02268-7/abstract

Individualised neoantigen therapy mRNA-4157 (V940 ... Patients with completely resected melanoma (stage IIIB–IV) were assigned 2:1 to receive open-label mRNA-4157 plus pembrolizumab or pembrolizumab ...

5. nyulangone.org nyulangone.org/news/perlmutter-cancer-center-clinical-trial-tests-personalized-mrna-vaccine-treating-metastatic-melanoma

Perlmutter Cancer Center Clinical Trial Tests Personalized ... In 24 subjects of 107 (22.4 percent), melanoma returned within three years of follow-up, compared with 20 out of 50 (40 percent) of those who ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06961006

A Clinical Study of V940 and Pembrolizumab (MK-3475) in ... The goal of this study is to learn if people who receive V940 with pembrolizumab live longer without the cancer growing or spreading than people who receive ...