mRNA-4106 + Checkpoint Inhibitors for Cancer

Not yet 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

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of a new treatment, mRNA-4106, for individuals with solid tumors, a type of cancer that forms in organs or tissues. The study consists of two parts: one tests mRNA-4106 alone, and the other tests it with checkpoint inhibitors, including Nivolumab and Relatlimab. It targets individuals with advanced cancer, such as melanoma or lung cancer, who have either tried other treatments or are beginning their first treatment for melanoma. Participants should have a measurable tumor and no active brain tumors. 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 treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot receive certain anticancer therapies or investigational agents within 14 days before starting the study treatment. It's best to discuss your current medications with the study team.

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

Research has shown that mRNA-4106 is currently being tested for safety in cancer treatment. As this is an early study, specific safety information is not yet available. This phase focuses on assessing how well participants tolerate the treatment and identifying any side effects.

For those receiving mRNA-4106 with nivolumab/relatlimab (another cancer treatment), some background information is available. Nivolumab/relatlimab has been used previously in cancer patients and may cause side effects, which can occur more frequently compared to using nivolumab alone.

Overall, these ongoing studies are crucial for understanding the safety of mRNA-4106, both alone and in combination with other treatments. Researchers will closely monitor participants to ensure their safety as they gather more information about these new treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about mRNA-4106 because it harnesses cutting-edge mRNA technology to target cancer. Unlike standard treatments like chemotherapy and radiation, which often attack both healthy and cancerous cells, mRNA-4106 is designed to stimulate the body’s immune system specifically against cancer cells. In combination with checkpoint inhibitors like nivolumab and relatlimab, mRNA-4106 could potentially enhance the immune response, offering a more targeted and powerful attack on tumors. This innovative approach could lead to more effective treatments with fewer side effects, which is a big step forward in cancer therapy.

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

Research has shown that mRNA-4106 uses a multivalent approach, targeting several cancer markers simultaneously, which could expand treatment options for cancer patients. In this trial, one group of participants will receive mRNA-4106 alone, while another group will test mRNA-4106 combined with Nivolumab and Relatlimab. Early results suggest that combining mRNA-4106 with drugs like Nivolumab and Relatlimab might enhance the immune system's ability to fight cancer. Previous studies have demonstrated that using Nivolumab and Relatlimab together has been effective, with an 80% survival rate without major events over four years in some patients with advanced melanoma. Although mRNA-4106 is still under investigation, combining it with these proven drugs appears promising for improving outcomes in solid tumor cases. ^{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

I am fully active and can carry on all pre-disease activities without restriction.

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.

Exclusion Criteria

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.

I have active brain tumors or cancer that has spread to my brain.

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

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

8 weeks

Dose Confirmation

Participants receive mRNA-4106 in combination with nivolumab/relatlimab at a standard dose

8 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 observe how patients tolerate these treatments and their effects on the cancer.

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 144 breast cancer patients, PD-L1 expression was found more frequently in triple negative breast cancer (TNBC) patients, suggesting that these patients may benefit from PD-L1 inhibition therapy due to their resistance to standard chemotherapy.

The study found no significant difference in soluble PD-L1 serum levels between breast cancer patients and healthy women, indicating that low serum levels of sPD-L1 are unlikely to interfere with PD-L1 inhibition therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients with breast cancer: TNBC versus TPBC. Yazdanpanah, P., Alavianmehr, A., Ghaderi, A., et al.[2021]

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]

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 65 patients with various cancers treated with PD1-targeting antibodies, specific immune-related gene expressions were identified that correlated with better responses to treatment and longer progression-free survival (PFS).

The findings suggest that measuring preexisting immune responses through mRNA expression patterns can reliably predict clinical outcomes in patients receiving PD1 therapy, regardless of cancer type or the specific antibody used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Gene Expression Profiling After PD-1 Blockade in Non-Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma. Prat, A., Navarro, A., Paré, L., et al.[2022]

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 Research shows that combining immune checkpoint inhibitors like Nivolumab with other treatments can enhance the immune system's ability to fight cancer.

5. mdanderson.org mdanderson.org/newsroom/research-newsroom/-esmo-2025--mrna-based-covid-vaccines-generate-improved-response.h00-159780390.html

ESMO 2025: mRNA-based COVID vaccines generate ... In the first group, 180 patients with advanced non-small cell lung cancer who received a vaccine had a median survival of 37.33 months, compared ...

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. trial.medpath.com trial.medpath.com/news/42c8807d00b05c51/moderna-advances-oncology-pipeline-with-first-dosing-in-phase-1-trial-of-novel-mrna-cancer-therapy

Moderna Advances Oncology Pipeline with First Dosing in ... Moderna has initiated dosing of mRNA-4106, an innovative cancer therapy candidate, in a Phase 1 clinical trial, marking a significant step in expanding its ...