V940 + Pembrolizumab for Skin Cancer

(INTerpath-007 Trial)

Not currently recruiting at 121 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Anti-PD-1, Anti-PD-L1, Anti-PD-L2, CTLA-4

Disqualifiers: Other skin cancer, Metastatic disease, Immunodeficiency, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with advanced cutaneous squamous cell carcinoma (cSCC). It seeks to determine if combining a personalized therapy, intismeran autogene, with pembrolizumab (an immune therapy) before and after surgery is more effective than standard treatment. Participants will be divided into groups to receive either this combination, pembrolizumab alone, or standard care, which typically involves surgery. The trial seeks individuals whose cSCC can be surgically removed and who do not have cancer that has spread to distant parts of the body.

As a Phase 2, Phase 3 trial, it measures the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer therapy advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop it 7 days before the first dose of the study medication. It's best to discuss your specific medications with the trial team.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop these at least 7 days before the first dose of the study medication.

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

Earlier studies have shown that the combination of V940 and pembrolizumab offers promising safety results. Research indicates that most people tolerate this combination well. Some patients experienced side effects, but these were usually mild and manageable.

Pembrolizumab, already approved by the FDA for other cancer treatments, also has a strong safety record. Long-term data suggest it is safe for many cancer patients, with serious side effects being rare.

Overall, both treatments have been tested in other trials and have demonstrated a good safety profile. While all treatments carry risks, the available data support the safety of these therapies for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care options for skin cancer, which typically involve surgery and possibly radiation, the investigational treatments in this trial focus on a combination of immunotherapies. Intismeran autogene is a novel component being tested alongside pembrolizumab. This combination is believed to enhance the immune system's ability to target and destroy cancer cells more effectively. Researchers are particularly excited about the potential of this approach because it could offer a more personalized and potent method of treatment, potentially improving outcomes for patients with skin cancer.

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

Research has shown that using intismeran autogene with pembrolizumab, which participants in this trial may receive, may help lower the chance of cancer recurrence. One study found that this combination reduced the risk of recurrence by 49%. This suggests it might be more effective at preventing cancer from returning than pembrolizumab alone, which is another treatment option in this trial. Pembrolizumab alone has been proven to help people with advanced melanoma live longer, with many patients experiencing tumor shrinkage. These findings suggest that both treatments could effectively manage advanced skin cancers. ^{1 5 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 a specific type of skin cancer called locally advanced cutaneous squamous cell carcinoma (LA cSCC) that can be surgically removed. Participants must not be pregnant or breastfeeding and should use effective contraception if applicable. They need to have a life expectancy over 3 months, good performance status, and proper organ function.

Inclusion Criteria

My skin cancer is confirmed and can be surgically removed.

My skin cancer is at an advanced stage but hasn't spread to distant parts.

My skin cancer can be removed with surgery aimed at curing it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive intismeran autogene and pembrolizumab as neoadjuvant therapy prior to surgery

6-12 weeks

Every 3-6 weeks (in-person)

Surgery

Participants undergo surgical resection as per local guidelines

Adjuvant Treatment

Participants receive intismeran autogene and pembrolizumab as adjuvant therapy following surgery

Up to 21 weeks

Every 3-6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 59 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 versus standard care alone or pembrolizumab alone in LA cSCC patients. It's given before and after surgery to see if it improves event-free survival compared to the usual treatment.

How Is the Trial Designed?

Group I: Pembrolizumab with SOC Experimental Treatment 2 Interventions

Participants will receive pembrolizumab 400 mg IV infusion q6w up to 12 weeks as neoadjuvant therapy prior to surgery.

Group II: Pembrolizumab plus Intismeran autogene with SOC Experimental Treatment 3 Interventions

Participants will receive intismeran autogene 1 mg intramuscular (IM) injection every 3 weeks (q3w) for up to 6 weeks and pembrolizumab 400 mg intravenous (IV) infusion every 6 weeks (q6w) up to 12 weeks as neoadjuvant therapy prior to surgery; followed by intismeran autogene 1 mg IM injection q3w up to 21 weeks.

Group III: Standard of Care (SOC) Active Control 1 Intervention

Participants will receive surgical resection as per local guidelines with/without adjuvant radiation therapy (RT) at investigator's discretion.

V940 is already approved in United States for the following indications:

Approved in United States as mRNA-4157/V940 for:

• High-risk melanoma following complete resection

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

Moderna TX

Collaborator

Trials

1

Recruited

1,000+

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 (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[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]

In a study of 39 patients with unresectable cutaneous squamous cell carcinomas (CSCCs), first-line treatment with pembrolizumab showed an objective response rate of 41% at week 15, indicating significant anti-tumor activity, especially in patients with PD-L1 positive tumors (55% response rate).

The treatment was generally well-tolerated, with 71% of patients experiencing adverse events, but only 7% had severe (grade ≥ 3) side effects, suggesting that pembrolizumab has a manageable safety profile while providing durable responses in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas. Maubec, E., Boubaya, M., Petrow, P., et al.[2021]

Pembrolizumab was found to be safe and well tolerated in a phase I study involving 20 patients with advanced solid tumors, with no dose-limiting toxicities observed at doses up to 10 mg/kg every 2 weeks.

The treatment demonstrated durable antitumor activity, with complete responses in two patients and stable disease in 15 others, indicating that a minimum effective dose for antitumor activity is 2 mg/kg every 3 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Patnaik, A., Kang, SP., Rasco, D., et al.[2022]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

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]

In a phase 3 trial involving 1019 patients with resected high-risk stage III melanoma, pembrolizumab significantly improved distant metastasis-free survival at 3.5 years, with 65.3% of patients in the pembrolizumab group remaining free of distant metastasis compared to 49.4% in the placebo group (HR 0.60).

The study also showed that pembrolizumab led to longer recurrence-free survival, with 59.8% of patients in the pembrolizumab group remaining free of recurrence compared to 41.4% in the placebo group, reinforcing its efficacy as an adjuvant therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Eggermont, AMM., Blank, CU., Mandalà, M., et al.[2021]

In a phase II trial involving 159 patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma, pembrolizumab showed significant antitumor activity, with an objective response rate of 50.0% in the locally advanced cohort and 35.2% in the recurrent/metastatic cohort.

The treatment demonstrated a manageable safety profile, with only 11.9% of patients experiencing grade 3-5 treatment-related adverse events, indicating that pembrolizumab is a promising and durable treatment option for cSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial. Hughes, BGM., Munoz-Couselo, E., Mortier, L., et al.[2022]

Citations

1. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10419154/

Efficacy of Pembrolizumab in Advanced Melanoma Specifically, in the KEYNOTE-001 study on advanced melanoma, pembrolizumab monotherapy resulted in a 3-year overall survival (OS) of 41% in patients previously ...

3. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma ...

4. keytruda.com keytruda.com/melanoma/advanced/

is an fda-approved treatment for advanced melanoma The cancer did not progress in 43% of people who received KEYTRUDA compared to 32% of people who received ipilimumab. More people saw tumors shrink.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01704287

NCT01704287 | Study of Pembrolizumab (MK-3475) ... This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL)

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40587032/

Real-World Outcomes of Pembrolizumab in Advanced ... This study aimed to assess real-world outcomes of pembrolizumab in patients with advanced melanoma in Australia.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11873308/

Long-Term Data From Patients Who Received ... The four patients with CSCC treated with pembrolizumab achieved either CR (n = 3) or stable disease (SD) (n = 1) as the best objective response according to ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.