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

Trial Summary

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.

What data supports the effectiveness of the drug mRNA-4106 + Nivolumab/Relatlimab for solid tumors?

Research shows that checkpoint inhibitors, like Nivolumab, are effective in certain cancers, such as metastatic colorectal cancer with high microsatellite instability (MSI-H) and non-small cell lung cancer, suggesting potential benefits for other solid tumors. ^{1 2 3 4 5}

What safety data exists for mRNA-4106 and checkpoint inhibitors like Nivolumab/Relatlimab in humans?

Immune checkpoint inhibitors, like Nivolumab, can cause side effects such as skin rash, fatigue, and autoimmune reactions (where the immune system attacks normal tissues). In a study of Chinese patients, 84.1% experienced some side effects, with 20.9% having severe reactions, and 0.8% had treatment-related deaths. Combining these drugs with other treatments can increase the risk of severe side effects. ^{6 7 8 9 10}

What makes the mRNA-4106 treatment unique for solid tumors?

The mRNA-4106 treatment is unique because it combines mRNA technology with checkpoint inhibitors to potentially enhance the immune system's ability to fight solid tumors. This approach may help overcome resistance to traditional PD-1 blockade therapies by restoring T cell function and reducing exhaustion, which is not typically achieved with standard treatments. ^{9 11 12 13 14}

What is the purpose of this trial?

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 participants with solid tumors.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Analysis of soluble programmed death-1 ligand-1 of lung cancer patients with different characteristics. [2023]

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

High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. [2022]

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

Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes. [2022]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Association of programmed death ligand 1 expression with prognosis among patients with ten uncommon advanced cancers. [2023]

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

Landscape of immune checkpoint inhibitor-related adverse events in Chinese population. [2021]

7. China 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. [2023]

8. France pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

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

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. [2021]

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

In situ vaccination with defined factors overcomes T cell exhaustion in distant tumors. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Role of PCIF1-mediated 5'-cap N6-methyladeonsine mRNA methylation in colorectal cancer and anti-PD-1 immunotherapy. [2023]

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

Sufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity. [2020]

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

IL10 Release upon PD-1 Blockade Sustains Immunosuppression in Ovarian Cancer. [2022]