mRNA-4359 + Pembrolizumab for Solid Cancers

Recruiting at 28 trial locations

Overseen By Moderna WeCare Team

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ModernaTX, Inc.

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

Disqualifiers: CNS tumors, Active infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 27 weeks

361 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of mRNA-4359, an experimental treatment, used alone or with pembrolizumab (an immunotherapy drug) or other drugs for various advanced cancers. It targets individuals with advanced melanoma or non-small-cell lung cancer (NSCLC). Those whose cancer has progressed after prior treatments may qualify. The trial aims to assess the treatment's safety and its potential to manage these cancers. Participants will receive combinations of these new treatments to determine the most effective approach. As a Phase 1, Phase 2 trial, it focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial protocol does not clearly specify if you must stop taking your current medications. However, you cannot have received certain anticancer therapies or investigational agents within 14 days before starting the study. It's best to discuss your specific 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-4359 is being tested for safety both alone and in combination with other treatments. Early results suggest that mRNA-4359 might benefit patients with advanced solid cancers, indicating potential safety as a treatment. However, further details about its safety are still under investigation.

When combined with pembrolizumab, studies suggest mRNA-4359 may aid melanoma patients who did not respond to previous treatments. Pembrolizumab, also known as Keytruda, is already used in various cancer treatments and has a known safety record, though it can cause side effects like tiredness, cough, and nausea.

Specific safety information for the combination of mRNA-4359 with ipilimumab and nivolumab is limited. However, nivolumab and ipilimumab have been studied together in other contexts and are generally considered safe, though they can also cause side effects.

Overall, since this trial is in its early stages, it primarily focuses on assessing safety. The treatments are being evaluated for tolerance and potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about mRNA-4359, especially when combined with pembrolizumab, because it introduces an innovative approach to treating solid cancers like melanoma and non-small cell lung carcinoma (NSCLC). Unlike standard treatments, which often involve chemotherapy or targeted therapies, mRNA-4359 leverages mRNA technology to potentially boost the immune system's ability to fight cancer cells directly. This technology allows for a more precise targeting of cancer cells, potentially leading to fewer side effects and improved outcomes. Combining mRNA-4359 with pembrolizumab, a well-known immune checkpoint inhibitor, may enhance the effectiveness of the treatment by further activating the body's immune response against cancer.

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

Research shows that mRNA-4359, when combined with pembrolizumab, has potential in treating certain cancers. In this trial, some participants will receive this combination, which previous studies have shown to help 24% of patients by shrinking or stopping tumor growth. Specifically, it was 67% effective in patients with PD-L1 positive melanoma, a type of skin cancer. Other participants will receive mRNA-4359 alone, which early results suggest may benefit patients with advanced solid cancers by targeting specific immune and cancer cells. This treatment aims to enhance the immune system's ability to attack cancer. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including specific types of lung cancer and melanoma. Participants must have measurable disease, be previously treated or offered targeted therapy (if applicable), and have a performance status indicating they are relatively active. Pregnant women, those with central nervous system metastases, unresolved toxicities from prior treatments, or significant medical conditions that could affect safety or compliance are excluded.

Inclusion Criteria

Dose Expansion Arm (Arm 2) only: Participant has histologically confirmed locally advanced, metastatic melanoma, or locally advanced or metastatic NSCLC with a PD-L1 TPS of ≥50% and with no EGFR or ALK positive tumor mutations, with measurable disease as determined by RECIST v1.1 and have not had any prior therapy for this cancer in this setting (that is, first line therapy). Must have a tumor lesion amenable to biopsy and must provide tumor biopsy sample at baseline (archival formalin-fixed, paraffin-embedded [FFPE]. If the participant is undergoing a new biopsy, they must have another lesion that can be followed for response. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1. Participant has adequate hematological and biological function

I have advanced cancer and my previous treatments didn't work or weren't suitable for me.

I have melanoma or NSCLC that didn't respond to checkpoint inhibitors, with a tumor that can be biopsied.

Exclusion Criteria

I agree to use condoms or not donate sperm during and up to 120 days after treatment.

My side effects from previous cancer treatments are mild or back to normal, except for hair loss or skin changes.

Participant has concurrent enrollment in another clinical study (unless it is an observational noninterventional clinical study) or during the follow-up period of an interventional study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mRNA-4359 alone or in combination with pembrolizumab for up to nine 21-day cycles

27 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

27 months

What Are the Treatments Tested in This Trial?

Interventions

• mRNA-4359
• Pembrolizumab

Trial Overview The study tests mRNA-4359 alone and combined with pembrolizumab to evaluate their safety in treating advanced solid tumors. It involves participants who've had standard treatments but still show progression of the disease. The trial will include biopsies to assess response to these interventions.

How Is the Trial Designed?

Group I: Pharmacodynamic (PD) Arm (Group 1): mRNA-4359 in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Participants with locally advanced or metastatic, and CPI refractory melanoma will be administered mRNA-4359 at an applicable dose in combination with pembrolizumab.

Group II: PD Arm (Group 2): mRNA-4359 in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Participants with locally advanced or metastatic, and CPI refractory NSCLC with a PD-L1 TPS ≥1% will be administered mRNA-4359 at an applicable dose in combination with pembrolizumab.

Group III: Arm 2d (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Participants 12 years or older with CPI refractory, advanced/metastatic melanoma with a PD-L1 TPS of ≥1% who have had progression on at least 1 prior CPI-based systemic therapy in the advanced/metastatic disease setting will be administered mRNA-4359 at an applicable dose in combination with pembrolizumab.

Group IV: Arm 2c (Dose Expansion): mRNA-4359 in Combination with Ipilimumab and Nivolumab Experimental Treatment 2 Interventions

Adult participants with locally advanced or metastatic melanoma who have not yet received any prior systemic therapy in this setting will be administered mRNA-4359 at an applicable dose in combination with ipilimumab and nivolumab.

Group V: Arm 2b (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab Experimental Treatment 3 Interventions

Adult participants with locally advanced or metastatic NSCLC with a PD-L1 TPS of ≥50%, with no known epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)-positive tumor mutations who have not yet received any prior systemic therapy for their NSCLC will be administered mRNA-4359 at an applicable dose in combination with pembrolizumab.

Group VI: Arm 2a (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Adult participants with locally advanced or metastatic melanoma who have not yet received any prior systemic therapy for their melanoma in this setting will be administered mRNA-4359 at an applicable dose in combination with pembrolizumab.

Group VII: Arm 1b (Melanoma Expansion Cohort): mRNA-4359 in Combination With Pembrolizumab Experimental Treatment 2 Interventions

Participants 18 years or older with CPI refractory, advanced/metastatic melanoma with a programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1% who have had progression on at least 1 prior CPI-based systemic therapy in the advanced/metastatic disease setting will be administered mRNA-4359 at an applicable dose in combination with pembrolizumab.

Group VIII: Arm 1b (Dose Confirmation): mRNA-4359 in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Participants with locally advanced or metastatic, and checkpoint inhibitor (CPI) refractory melanoma or locally advanced or metastatic, and CPI refractory non-small-cell lung carcinoma (NSCLC) will be administered mRNA-4359 at an applicable dose in combination with pembrolizumab.

Group IX: Arm 1a (Dose Escalation): mRNA-4359 Alone Experimental Treatment 1 Intervention

Adult participants with locally advanced or metastatic cancer will be administered mRNA-4359 at an applicable 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 phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase 1a/b trial involving 26 patients with PD-L1-positive non-small cell lung cancer (NSCLC), the combination of ramucirumab and pembrolizumab showed a manageable safety profile, with 84.6% experiencing treatment-related adverse events, primarily hypertension.

The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression (TPS ≥ 50%), who had a median progression-free survival that was not reached.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Herbst, RS., Arkenau, HT., Bendell, J., et al.[2023]

Pembrolizumab (Keytruda) received FDA accelerated approval for treating recurrent gastric or gastroesophageal junction adenocarcinoma in patients whose tumors express PD-L1, based on a multicenter trial involving 259 patients, showing a 13.3% overall response rate.

The treatment was associated with common side effects like fatigue and decreased appetite, and serious adverse reactions included pneumonia and pulmonary embolism, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1. Fashoyin-Aje, L., Donoghue, M., Chen, H., et al.[2021]

In a study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[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]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

Citations

1. trials.modernatx.com trials.modernatx.com/study/?id=mRNA-4359-P101

A Clinical Trial of a Cancer Treatment for Adults with Solid ... In this trial, Moderna is researching the use of mRNA-4359 to see if it will instruct the body to target certain immune cells and cancer cells to slow or ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05533697

NCT05533697 | Study of mRNA-4359 Administered Alone ... The primary goal of this study is to assess the safety and tolerability of mRNA-4359 administered alone and in combination with pembrolizumab.

3. targetedonc.com targetedonc.com/view/cancer-antigen-mrna-4359-shows-increased-efficacy-in-patients-with-melanoma

Cancer Antigen mRNA-4359 Shows Increased Efficacy in ... mRNA-4359 combined with pembrolizumab achieved a 24% ORR and 67% efficacy in PD-L1 positive melanoma patients. · The study involved 29 patients, ...

4. news-medical.net news-medical.net/news/20240916/Early-data-shows-mRNA-4359-may-benefit-patients-with-advanced-solid-cancers.aspx

Early data shows mRNA-4359 may benefit patients with ... Interim data from the Phase I dose escalation part of the mRNA cancer immunotherapy (mRNA-4359), show promise in patients with advanced solid cancers.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS2676

Phase 1/2 study of mRNA-4359 administered alone and in ... mRNA-4359 encodes immunogenic peptides proposed to generate anti-PD-L1/IDO1-specific T-cells to kill immunosuppressive regulatory cells as well ...