mRNA Vaccine + Immunotherapy for Melanoma

Recruiting at22 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: ModernaTX, Inc.

Must be taking: Pembrolizumab

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if a combination of a personalized cancer vaccine (mRNA-4157) and an immune-boosting medication (pembrolizumab) can better prevent melanoma from returning in patients who have had their tumors surgically removed. Pembrolizumab has been shown to help prevent the return and spread of melanoma in patients who have had their tumors surgically removed.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic steroid therapy or any other immunosuppressive therapy within 7 days before starting the trial.

What data supports the effectiveness of the mRNA-4157/V940 and pembrolizumab treatment for melanoma?

Research shows that the combination of the mRNA-4157/V940 vaccine and pembrolizumab significantly reduces the risk of melanoma coming back after surgery, compared to using pembrolizumab alone. ^{1 2 3 4 5}

Is the mRNA Vaccine + Immunotherapy for Melanoma safe for humans?

Pembrolizumab (also known as KEYTRUDA) has been used in treating melanoma and is generally well-tolerated, but it can cause side effects like fatigue, rash, itching, and diarrhea. Some less common but serious side effects include immune-related issues like thyroid problems, lung inflammation, and liver inflammation. More studies are needed to fully understand the safety of combining it with mRNA vaccines. ^{6 7 8 9 10}

How is the mRNA Vaccine + Pembrolizumab treatment for melanoma different from other treatments?

This treatment is unique because it combines an mRNA vaccine, which helps the immune system recognize and attack melanoma cells, with pembrolizumab, a drug that boosts the immune response by blocking a protein that prevents immune cells from attacking cancer. This combination aims to enhance the body's ability to fight melanoma more effectively than using pembrolizumab alone. ^{1 4 6 11 12}

Research Team

Eligibility Criteria

This trial is for individuals who've had surgery to remove melanoma that spread to a lymph node and are at high risk of the cancer coming back. They should have no current evidence of disease, be in good physical condition (able to perform daily activities or light work), and have normal organ/marrow function. People with prior cancers, recent vaccines, blood transfusions, infections needing treatment, HIV/hepatitis B/C, autoimmune diseases or immunosuppression can't join.

Inclusion Criteria

I had surgery to remove my cancer completely within the last 13 weeks.

My skin cancer has spread to a lymph node and is likely to come back.

I am currently free of cancer after surgery, with no signs of it returning or spreading.

Exclusion Criteria

I have not taken steroids or immunosuppressants in the last week.

I have not received a live vaccine in the last 30 days.

I have not had a blood transfusion or received colony-stimulating factors in the last 2 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 9 doses of mRNA-4157 and pembrolizumab every 21 days, or pembrolizumab alone every 21 days, for up to 18 cycles (approximately 1 year)

1 year

Follow-up

Participants are monitored for recurrence-free survival and distant metastasis-free survival using radiological imaging

Up to 5 years

Treatment Details

Interventions

• mRNA-4157 (Cancer Vaccine)
• Pembrolizumab (Checkpoint Inhibitor)

Trial Overview The study is testing if adding a personalized cancer vaccine called mRNA-4157 to pembrolizumab (a known immune therapy) after surgery can prevent melanoma from returning better than pembrolizumab alone. Participants will either receive the combination treatment or just pembrolizumab.

Participant Groups

Group I: mRNA-4157 and Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive up to 9 doses of mRNA-4157 (every 21 days). Participants may continue on pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.

Group II: Pembrolizumab Active Control 1 Intervention

Participants will receive pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.

Who Is Running the Clinical Trial?

ModernaTX, Inc.

Lead 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

Merck Sharp & Dohme LLC

Industry 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

Findings from Research

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]

In a phase III trial involving 1,019 patients with resected high-risk stage III melanoma, pembrolizumab significantly prolonged recurrence-free survival (RFS) compared to placebo, with a 3-year RFS rate of 63.7% versus 44.1%.

The benefits of pembrolizumab were consistent across various patient subgroups, including those with different tumor stages and BRAF mutation statuses, indicating its broad efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial. Eggermont, AMM., Blank, CU., Mandala, M., et al.[2023]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., et al.[2022]

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]

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]

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]

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 (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]

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]

The study confirms that PD-1 inhibitors like Pembrolizumab and Nivolumab improve response and survival rates in advanced melanoma patients, especially when combined with the CTLA-4 inhibitor Ipilimumab, which shows superior efficacy compared to monotherapies.

However, these immunotherapies are associated with significant immune-related adverse events, some of which can be life-threatening, highlighting the need for further studies to better understand their safety profiles and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. Schaefer, A., Sachpekidis, C., Diella, F., et al.[2020]

In a phase I/II trial involving 31 metastatic melanoma patients, a dendritic cell vaccine targeting patient-specific neoantigens showed a favorable safety profile with no serious adverse events and demonstrated a significant survival benefit compared to matched controls (1-year survival of 43% vs. 24%).

The vaccine elicited a tumor-specific immune response in 16 out of 31 patients, with a higher response rate observed after intradermal vaccination (80%) compared to intranodal (38%), suggesting that this approach could be combined with other treatments for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells. Kyte, JA., Aamdal, S., Dueland, S., et al.[2021]

The study involved 21 metastatic melanoma patients and demonstrated that intradermal injection of protamine-stabilized mRNA vaccines is safe, with no serious adverse events observed.

The treatment led to a significant reduction in immunosuppressive cells and an increase in vaccine-directed T cells in some patients, with one patient achieving a complete response, suggesting potential efficacy and warranting further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. Weide, B., Pascolo, S., Scheel, B., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

KEYNOTE - D36: personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma. [2022]

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

Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. [2022]

4. 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]

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

mRNA Vaccine Slows Melanoma Recurrence. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

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

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. [2020]

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

Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells. [2021]

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

Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. [2017]