mRNA-4106 + Checkpoint Inhibitors for Solid Tumors

Recruiting at 2 trial locations

Overseen By Moderna WeCare Team

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ModernaTX, Inc.

Must not be taking: Chemotherapy, Hormonal therapy, Biologic therapy, Immunotherapy

Disqualifiers: CNS tumors, Unstable illness, others

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

Compensation: Varies

Number of Visits: Unknown

57 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of a new treatment called mRNA-4106 for individuals with certain advanced or hard-to-treat cancers. The study tests this treatment both alone and in combination with two existing cancer drugs, nivolumab and relatlimab, to assess how well these treatments are tolerated. Individuals who have exhausted all standard cancer treatments or have untreated, inoperable melanoma might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as other cancer treatments or investigational drugs, at least 14 days before starting the study. If you're on immunosuppressive steroids, you may need to stop or reduce them to 10 mg of prednisone or less per day.

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

Research is currently testing mRNA-4106 to determine its safety when used alone or with other drugs like nivolumab and relatlimab. As mRNA-4106 is in the early testing stages, complete safety information is not yet available. However, researchers carefully monitor for any side effects to ensure safety for participants.

Nivolumab and relatlimab have already received approval for treating certain types of cancer. Previous studies have shown that these drugs can cause side effects, some of which might not appear on the labels. While generally considered safe, researchers will still monitor for any new or serious issues when combined with mRNA-4106.

In summary, although mRNA-4106 is still under investigation, the established use of nivolumab and relatlimab provides some reassurance about safety. Participants in this study will be closely monitored to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about mRNA-4106 because it represents a novel approach to treating solid tumors. Unlike traditional cancer treatments like chemotherapy or radiation, which can damage healthy cells, mRNA-4106 uses messenger RNA technology to instruct the body to produce specific proteins that help fight cancer cells. In combination with checkpoint inhibitors like nivolumab and relatlimab, mRNA-4106 aims to enhance the immune system's ability to detect and destroy cancer cells more effectively. This innovative mechanism could lead to more precise and potentially less harmful cancer treatment options.

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

This trial will evaluate mRNA-4106 both as a standalone treatment and in combination with nivolumab and relatlimab. Studies have shown that using nivolumab and relatlimab together can significantly improve cancer treatment outcomes. One study found that these drugs helped delay cancer progression for a longer period. Another study showed that 80% of certain cancer patients experienced no major cancer-related events for four years after treatment.

Research suggests that mRNA-4106 is a new treatment designed to target several cancer markers simultaneously, potentially increasing its effectiveness against various cancer types. Although limited data exists on mRNA-4106's efficacy in humans, its design indicates potential effectiveness when combined with drugs like nivolumab and relatlimab. Participants in this trial will receive mRNA-4106 either alone or with nivolumab and relatlimab to assess its effectiveness. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with solid tumors, including uterine tumors. Participants should be adults who have a tumor that can be measured and are willing to provide tissue samples. They must not have had prior treatment with certain vaccines or gene therapies.

Inclusion Criteria

My blood and organ functions are within normal ranges.

Participants who could become pregnant: negative pregnancy test within 24 hours before the first dose of study treatment.

I have advanced cancer with a measurable tumor and have tried or refused all standard treatments.

Exclusion Criteria

Participant has concurrent enrollment in another clinical study (unless it is an observational noninterventional clinical study).

I haven't taken any prohibited cancer treatments or investigational drugs recently.

Participant has any unstable or clinically significant concurrent medical/psychiatric illness or social situation that would limit compliance with study requirements or compromise the ability of the participant to provide written informed consent, per the discretion of the Investigator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive mRNA-4106 at a test dose as monotherapy to assess safety and tolerability

8-12 weeks

Dose Confirmation

Participants receive mRNA-4106 in combination with nivolumab/relatlimab to confirm dosing and assess safety

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• mRNA-4106
• Nivolumab/Relatlimab

Trial Overview The study is testing the safety of mRNA-4106 alone and combined with immune checkpoint inhibitors Nivolumab/Relatlimab in treating solid tumors. It will assess how well patients tolerate these treatments.

How Is the Trial Designed?

Group I: Arm 2 (Dose Confirmation): mRNA-4106 in Combination with Nivolumab/Relatlimab Experimental Treatment 2 Interventions

Participants will receive mRNA-4106 at an applicable dose in combination with nivolumab/relatlimab at a standard dose.

Group II: Arm 1 (Dose Escalation): mRNA-4106 Alone Experimental Treatment 1 Intervention

Participants will receive mRNA-4106 at a test dose as monotherapy.

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

Published Research Related to This Trial

In a study of 581 cancer patients treated with PD-1/PD-L1 inhibitors, 20% experienced endocrine adverse events (AEs), with pembrolizumab showing a significantly higher incidence of 38.5%.

Patients who developed endocrine AEs had better overall response rates (33.3% vs. 23.1%) and disease control rates (91.1% vs. 79.1%), suggesting that these AEs may be associated with a more favorable treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world retrospective study of incidence and associated factors of endocrine adverse events related to PD-1/PD-L1 inhibitors. Wang, Z., Hu, C., Zhang, A., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Cancer immunotherapies, particularly anti-CTLA4 and anti-PD1/PD-L1, are becoming more common in treatment regimens, leading to increased exposure of patients to immune-related adverse events (irAEs).

These immunotherapies can activate the immune system to fight tumors effectively, but they also have a unique toxicity profile that can cause autoimmune reactions, necessitating changes in clinical management practices to address these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Laparra, A., Champiat, S., Michot, JM., et al.[2021]

In the phase 3 MYSTIC trial involving 1118 patients with metastatic non-small cell lung cancer, durvalumab did not significantly improve overall survival compared to chemotherapy, nor did the combination of durvalumab and tremelimumab show better outcomes than chemotherapy for patients with high PD-L1 expression.

However, patients with a blood tumor mutational burden (bTMB) of 20 or more mutations per megabase experienced significantly improved overall survival with durvalumab plus tremelimumab, suggesting that bTMB may be a useful biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. Rizvi, NA., Cho, BC., Reinmuth, N., et al.[2021]

In a study of 93 Chinese patients with advanced melanoma treated with PD-1 inhibitors, those who developed immune-related adverse events (irAEs) had significantly higher overall response rates (ORR) and disease control rates (DCR) compared to those without irAEs.

Patients experiencing three or more irAEs showed even better clinical outcomes, including longer progression-free survival and overall survival, suggesting that the presence of irAEs may indicate a more effective immune response to PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. Zhao, JJ., Wen, XZ., Ding, Y., et al.[2021]

In a study of 85 patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer treated with immune checkpoint inhibitors (ICIs), a higher number of tumor infiltrating lymphocytes (TILs) was significantly associated with better treatment responses and survival outcomes.

The research found that patients with a high number of TILs had a response rate of 70.6% and significantly improved progression-free survival and overall survival compared to those with low TILs, suggesting that TIL count could serve as a predictive biomarker for ICI efficacy in MSI-H mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes. Loupakis, F., Depetris, I., Biason, P., et al.[2022]

Soluble programmed death-1 ligand-1 (sPD-L1) levels were significantly higher in lung cancer patients compared to healthy controls, indicating its potential role as a biomarker for lung cancer.

Higher sPD-L1 levels were associated with more advanced stages of non-small cell lung cancer (NSCLC) and poorer overall health, suggesting that elevated sPD-L1 may indicate a negative prognosis for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of soluble programmed death-1 ligand-1 of lung cancer patients with different characteristics. Zhu, HB., Song, X.[2023]

Citations

1. targetedonc.com targetedonc.com/view/phase-1-trial-of-mrna-4106-begins-dosing-patients-with-solid-tumors

Phase 1 Trial of mRNA-4106 Begins Dosing Patients With ... A phase 1 trial of mRNA-4106 has dosed its first patient with an advanced or metastatic solid tumor.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06880536

NCT06880536 | A Study of mRNA-4106 Administered ... The purpose of this study is to assess the safety and tolerability of mRNA-4106 administered alone and in combination with checkpoint inhibitor (CPI) therapy ...

3. prnewswire.com prnewswire.com/news-releases/start-doses-first-us-patient-in-modernas-phase-1-clinical-trial-of-mrna-4106-a-pan-tumor-antigen-therapy-candidate-in-solid-tumors-302455728.html

START Doses First U.S. Patient in Moderna's Phase 1 ... mRNA-4106's multivalent approach aims to broaden treatment options for patients with cancer, advancing the field beyond single-targeted ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-2-2025-8f4bd

mRNA-4106 + Checkpoint Inhibitors for Cancer Trial Overview The study is testing the safety of mRNA-4106 alone and combined with immune checkpoint inhibitors Nivolumab/Relatlimab in treating solid tumors.

5. jitc.bmj.com jitc.bmj.com/content/13/Suppl_2/A1056.full.pdf

Abstracts tiple tumor types and HLA profiles, mRNA-4106 exemplifies an off-the-shelf strategy that balances immunologic breadth with clinical scalability. Methods ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06880536

A Study of mRNA-4106 Administered Alone and in ... The purpose of this study is to assess the safety and tolerability of mRNA-4106 administered alone and in combination with checkpoint inhibitor (CPI) therapy in ...

7. ainvest.com ainvest.com/news/moderna-mrna-4106-pioneering-future-pan-tumor-cancer-therapy-2505/

Moderna's mRNA-4106: Pioneering the Future of Pan ... The Phase 1 trial, initiated in May 2025, focuses on advanced or metastatic solid tumors—a patient population in desperate need of alternatives ...