V940 + Pembrolizumab for Skin Cancer

Recruiting at 107 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

1012 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a two-part (Phase 2/Phase 3) study of intismeran autogene, an individualized neoantigen therapy (INT), plus pembrolizumab in participants with locally resectable advanced cutaneous squamous cell carcinoma (LA cSCC). Phase 2 has three arms intismeran autogene plus pembrolizumab given as neoadjuvant and adjuvant treatment with standard of care (SOC), standard of care (surgical resection with/without adjuvant radiation therapy (RT) only at investigator's discretion) and pembrolizumab monotherapy given as neoadjuvant and adjuvant treatment with SOC. This phase will assess the safety and efficacy of intismeran autogene in combination with pembrolizumab as neoadjuvant and adjuvant therapy in participants with resectable LA cSCC as compared to standard of care SOC only. The primary hypothesis is that intismeran autogene plus pembrolizumab with SOC is superior to SOC only with respect to event free survival (EFS) as assessed by the investigator. Phase 3 expansion will be determined by prespecified Go-No-Go decision in which 412 additional participants will be randomized to intismeran autogene plus pembrolizumab with SOC and SOC only, without changing the inclusion/exclusion criteria for the additional enrollment or study endpoints.

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.

What data supports the idea that V940 + Pembrolizumab for Skin Cancer is an effective drug?

The available research shows that Pembrolizumab, when used alone, has been effective in treating various types of skin cancer. For instance, in a study comparing Pembrolizumab to a placebo for patients with resected stage III melanoma, it was found to improve the time patients lived without the cancer coming back. Another study showed that Pembrolizumab was better than another drug, ipilimumab, for advanced melanoma. Additionally, Pembrolizumab showed positive results in treating advanced cutaneous squamous cell carcinoma, with significant and lasting effects. These findings suggest that when combined with V940, Pembrolizumab could be an effective treatment for skin cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Pembrolizumab for skin cancer?

Research shows that Pembrolizumab is effective in improving survival and reducing recurrence in patients with advanced melanoma and cutaneous squamous cell carcinoma, making it a promising option for treating skin cancer. ^{1 2 3 4 5}

What safety data exists for the treatment V940 + Pembrolizumab for skin cancer?

Pembrolizumab, also known as KEYTRUDA or MK-3475, has been evaluated in multiple studies for its safety profile in treating advanced melanoma and other skin cancers. It is generally well-tolerated with a favorable safety profile. Common adverse events include fatigue, rash, itching, and diarrhea, while less frequent immune-related adverse events include hypothyroidism, colitis, hepatitis, and pneumonitis. In the KEYNOTE-030 expanded access program, 19.1% of patients experienced at least one treatment-related adverse event, with 3.1% experiencing grade 3/4 events. No treatment-related deaths were reported. These findings support the use of pembrolizumab for patients with advanced melanoma. ^{5 6 7 8 9}

Is the combination of V940 and Pembrolizumab safe for treating skin cancer?

Pembrolizumab, also known as KEYTRUDA, has been shown to have a favorable safety profile in treating advanced melanoma and other skin cancers. Common side effects include tiredness, rash, itching, and diarrhea, while less common effects can include thyroid issues, inflammation of the colon, liver, or lungs. No treatment-related deaths were reported in the studies. ^{5 6 7 8 9}

Is the drug V940 a promising treatment for skin cancer?

Yes, V940, also known as mRNA-4157, is a promising treatment for skin cancer when used with Pembrolizumab. Pembrolizumab is a drug that helps the immune system fight cancer cells more effectively. It has shown strong and lasting effects in treating skin cancer, making the combination with V940 a hopeful option for patients. ^{1 3 5 10 11}

What makes the V940 + Pembrolizumab drug unique for skin cancer?

The V940 + Pembrolizumab drug is unique because it combines an mRNA-based vaccine (V940) with pembrolizumab, a monoclonal antibody that helps the immune system attack cancer cells by blocking the PD-1 receptor on T cells. This combination aims to enhance the body's immune response against skin cancer, offering a novel approach compared to traditional treatments. ^{1 3 5 10 11}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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; followed by pembrolizumab 400 mg IV infusion q6w or until discontinuation.

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 and pembrolizumab 400 mg IV infusion q6w or until discontinuation.

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas. [2021]

2. England 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

5. England 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. [2022]