Breakthrough Clinical Results
Moderna announced that three abstracts on its investigational mRNA therapeutics will be presented at the 2025 European Society for Medical Oncology (ESMO) Congress. This includes data from a mini oral presentation on mRNA-4359, an mRNA-based therapy designed to elicit T-cell immune responses against tumor and immunosuppressive cells, in combination with pembrolizumab for checkpoint inhibitor-resistant/refractory melanoma. Two poster presentations will feature data on intismeran autogene (V940/mRNA-4157), jointly developed with Merck, in high-risk non-muscle-invasive bladder cancer and as a first-line therapy for advanced melanoma.
Key Highlights
- Three abstracts on Moderna's investigational mRNA therapeutics accepted for presentation at ESMO Congress 2025.
- Mini oral presentation on mRNA-4359 plus pembrolizumab in checkpoint inhibitor-resistant/refractory melanoma.
- Poster presentations on intismeran autogene (V940/mRNA-4157) in high-risk non-muscle-invasive bladder cancer and advanced melanoma.
- Moderna will host an analyst event at ESMO.
Drug used in other indications
mRNA-4359 and Pembrolizumab Clinical Trials Beyond Melanoma
Based on a comprehensive review of available information, there is no data to indicate that the combination therapy of mRNA-4359 and Pembrolizumab is currently being trialed for indications other than melanoma.
While Pembrolizumab as a monotherapy has established clinical applications across multiple cancer types, the specific combination with mRNA-4359 does not appear to have documented clinical trials for indications beyond melanoma at this time.
It's worth noting that other mRNA therapies, such as mRNA-4157 (V940), have been studied in combination with Pembrolizumab for melanoma treatment, but this should not be confused with mRNA-4359.
Without specific trial information for other indications, details regarding intervention models, treatment protocols, or study designs for mRNA-4359 and Pembrolizumab combination therapy beyond melanoma cannot be provided.
The field of mRNA-based immunotherapies is rapidly evolving, and future clinical trials may expand to investigate this combination therapy's efficacy in treating other cancer types beyond melanoma.
Incidence and Prevalence
Latest Estimates of Melanoma Incidence and Prevalence
The global burden of melanoma continues to show significant variation across regions, with recent data revealing important trends in both incidence and mortality.
Global Incidence
Worldwide, melanoma accounted for approximately 132,000 cases per year as reported in 2015. In stark contrast, Japan experiences a much lower burden with only 1500-2000 cases per year, highlighting the significant geographic variation in melanoma risk.
Recent Trends
The most recent data from 2020 shows encouraging developments in melanoma outcomes in the United States, with mortality rates decreasing by 17.9% from 2013 to 2016. This represents an annual percent change of -6.2%, with particularly sharp declines observed among men aged 50 years or older (annual percent change of -8.3%). This multiyear decline is described as the largest and most sustained improvement in melanoma mortality ever observed and is unprecedented in cancer medicine.
Regional Variations
Several regional studies provide insight into melanoma patterns:
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In Turkey (2015), a study of 1574 patients found that 92% of cases were invasive melanoma and 8% were in-situ melanoma, with superficial spreading melanoma (37.9%) being the most common type.
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Australia (2011) demonstrated that while incidence of thin melanomas stabilized between 1996 and 2006, thick melanomas continued to increase (males +2.6%; females +1.6%). A strong latitude gradient was observed with highest rates in northern, more tropical areas.
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In Florida (2010), melanoma incidence rates increased by 3.0% per year among White non-Hispanic men, 3.6% among White non-Hispanic women, and 3.4% among White Hispanic women. Both White Hispanics and blacks had significantly more advanced melanoma at presentation.
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Spain (2008) reported a 92% increase in new melanoma cases between 1990-1996 and 1997-2005.
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Historical data from Sweden (1978) noted a 7% annual increase in melanoma incidence between 1959 and 1968.
Demographic Patterns
The male/female ratio for melanoma has been reported as 1/1.5, indicating higher prevalence among women. The mean age at diagnosis was 56.7 years in the Turkish cohort.
These findings underscore the complex epidemiology of melanoma globally, with significant variations by geography, ethnicity, and time period, while recent mortality improvements in the US suggest progress in melanoma management.
Key Unmet Needs and Targeted Populations for Melanoma
Melanoma Subtypes with Unique Challenges
- Uveal melanoma (UM) represents a significant unmet need with no standard systemic treatment for disseminated disease
- UM is not BRAF-mutated, limiting treatment options, and immune checkpoint inhibitors are rarely effective due to low mutation burden
- Acral melanoma (AM) and acral lentiginous melanoma (ALM) have worse prognosis than other subtypes and show unsatisfactory response to current immune checkpoint inhibitors
- ALM is the most common melanoma subtype in non-Caucasians and exhibits a suppressive immune microenvironment
Racial and Ethnic Disparities
- Racial disparities persist despite advances in immune checkpoint inhibitors (ICIs)
- Patients in counties with higher proportion of minorities experience delays in ICI treatment
- Hispanic populations face particularly pronounced delays in treatment initiation
- Different ethnic groups show varying responses to PD-1 monotherapy across melanoma subtypes, with White patients showing significantly higher response rates in nonacral cutaneous melanomas compared to East Asian/Hispanic/African patients
Treatment-Resistant Populations
- The 5-year survival rate for advanced melanoma remains only around 50%
- High unmet need exists for patients who progress on immune checkpoint inhibitors
- Patients with PD-1 inhibitor-resistant melanoma are being studied with CD3ΞΆ as a potential biomarker
- Patients with high immune-related risk score (IRRS) may represent an immunotherapy-resistant population requiring alternative approaches
Rare and Aggressive Subtypes
- Mucosal melanoma patients have been excluded from most Phase III clinical trials
- Head and neck mucosal melanoma outcome data are scarce with unclear therapeutic efficacy of immune checkpoint inhibitors
- Nodular melanoma (NM) patients have significantly shorter distant metastasis-free survival compared to superficial spreading melanoma
- Liver-dominant metastatic uveal melanoma patients are being targeted with specialized treatments like percutaneous hepatic perfusion
Treatment Challenges
- Complex treatment selection for BRAF-mutant patients with multiple available options
- Ipilimumab/nivolumab benchmark treatment has a high toxicity profile, creating need for equally effective but less toxic options
- Adjuvant treatment choices are often driven by risk for toxicity rather than efficacy alone
- Patients treated with immune checkpoint inhibitors or BRAF/MEK inhibitors have higher risk of uveitis, indicating need for specialized management approaches