New York — A personalized Moderna cancer vaccine has met the main goals of a large Phase 3 trial in patients with high-risk melanoma. Moderna and Merck said the treatment reduced the risk of the cancer returning and helped prevent it from spreading to other parts of the body.
The experimental treatment, called intismeran autogene, combines a personalized messenger RNA vaccine with Keytruda, Merck’s cancer immunotherapy.
The Phase 3 INTerpath-001 trial included 1,157 patients with stage IIB, IIC, III or IV melanoma. All patients had undergone surgery to remove their tumors.
Researchers divided the participants into two groups. One group received the personalized vaccine with Keytruda. The other received Keytruda alone.
The study is still underway. However, the companies said the treatment met both its primary and key secondary goals. They also reported no new safety signals.
The results could mark an important step for personalized cancer treatment. Unlike a standard vaccine, this treatment is designed for each patient.
Doctors first analyze the mutations in a patient’s tumor. Researchers then use that information to create an individualized mRNA vaccine.
Moderna and Merck are now preparing for discussions with regulators. The companies expect to seek approval, although they have not announced a specific filing date.
The development also gives mRNA technology another major test. The technology became widely known through COVID-19 vaccines. However, researchers have studied its potential in cancer treatment for years.
How the Moderna Cancer Vaccine Works Against Melanoma
The Moderna cancer vaccine starts with the patient’s own tumor.
After surgery, researchers examine the tumor’s genetic mutations. They look for changes that can produce neoantigens. These are markers that may help the immune system distinguish cancer cells from healthy cells.
Scientists then select promising targets and design an mRNA sequence for the patient.
The vaccine uses that mRNA to give cells temporary instructions. Those instructions help the immune system recognize specific targets linked to the patient’s cancer.
The approach differs from a traditional vaccine.
A conventional vaccine usually has the same basic formulation for everyone. A personalized cancer vaccine uses information from each patient’s tumor instead.
The treatment also includes Keytruda, whose active ingredient is pembrolizumab. Keytruda blocks the PD-1 immune checkpoint. This can help immune cells remain active against cancer.
The two treatments therefore have different roles.
The personalized vaccine gives the immune system specific targets. Keytruda helps prevent the immune response from being switched off.
Keytruda is already an established treatment for melanoma. The US Food and Drug Administration has approved pembrolizumab for certain patients after melanoma has been completely removed through surgery. <a href=”https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adjuvant-treatment-melanoma” target=”_blank” rel=”noopener noreferrer”>FDA information on Keytruda for melanoma treatment</a>
The latest Phase 3 findings build on earlier clinical results.
A previous Phase 2b study produced encouraging long-term data. After five years, patients who received intismeran autogene with Keytruda had a 49% lower risk of recurrence or death than patients who received Keytruda alone.
The earlier results helped support the move to a larger Phase 3 study.
Melanoma is a useful testing ground for personalized cancer vaccines because melanoma cells can contain many genetic mutations. Some of those mutations may create targets that the immune system can recognize.
However, identifying those targets is only one part of the challenge.
Researchers must also determine which mutations are most likely to produce a strong immune response. They then need to create and deliver the individualized treatment quickly.
That makes personalized vaccines more complex than standard medicines.
The treatment is also being tested in a specific clinical setting. Patients in the Phase 3 study had already undergone surgery.
The goal is therefore different from shrinking a large tumor that is already visible. Instead, the treatment aims to eliminate or control microscopic cancer cells that may remain after surgery.
If those cells survive, they can later cause the cancer to return or spread.
Melanoma remains a significant health concern in the United States. The National Cancer Institute provides detailed information on melanoma diagnosis, treatment and ongoing research. <a href=”https://www.cancer.gov/types/skin/hp/melanoma-treatment-pdq” target=”_blank” rel=”noopener noreferrer”>National Cancer Institute melanoma treatment information</a>
Moderna is also testing personalized mRNA cancer treatments in other solid tumors.
The company’s oncology program includes research into personalized cancer vaccines and other therapies. The broader program could help determine whether the same technology can work against different types of cancer. <a href=”https://esus.trials.modernatx.com/oncology/” target=”_blank” rel=”noopener noreferrer”>Moderna oncology clinical research program</a>
That possibility is important because cancer varies greatly from one patient to another.
Two people with the same type of cancer can have different mutations. Even cells inside the same tumor can differ.
Personalized treatment aims to account for those differences.
Still, the melanoma results do not prove that the same approach will work equally well in every cancer. Each tumor type presents different biological and clinical challenges.
The Phase 3 findings instead provide evidence that personalized mRNA treatment can produce meaningful results in high-risk melanoma when combined with Keytruda.
Moderna’s Cancer Vaccine Could Transform Its mRNA Strategy
The melanoma results arrive at an important time for Moderna.
The company became one of the best-known names in biotechnology after the success of its COVID-19 vaccine. Since then, it has worked to expand its business into other areas.
Cancer is one of the most important parts of that strategy.
A successful personalized vaccine could give Moderna a new oncology product. More importantly, it could demonstrate that the company’s mRNA technology has uses beyond infectious diseases.
For Merck, the opportunity is closely linked to Keytruda.
Keytruda is already widely used to treat cancer. Combining it with a personalized vaccine could strengthen its role in melanoma treatment.
The strategy could also lead to new combinations for other solid tumors if future trials produce positive results.
There are, however, major challenges ahead.
Personalized cancer vaccines require a different manufacturing process from conventional medicines.
First, doctors must collect a tumor sample. Researchers then sequence the tumor and identify relevant mutations. Next, they design the vaccine and manufacture the individualized treatment.
Finally, the vaccine must reach the patient within an appropriate treatment window.
Every step must meet strict quality standards.
This process could make personalized vaccines more expensive and difficult to produce than standard drugs. Healthcare systems and insurers will also have to assess whether the clinical benefits justify the additional cost and complexity.
Regulatory approval is another important step.
The positive Phase 3 result does not mean that intismeran autogene is already an approved treatment. Regulators must review the complete clinical data before making a decision.
They will assess several factors, including effectiveness, safety and manufacturing quality.
The companies still need to provide the complete Phase 3 dataset. Researchers and regulators will then have an opportunity to examine the results in greater detail.
For Moderna, the announcement has already affected investor sentiment.
The company’s shares rose sharply after the news. Investors are now assessing whether oncology could become a significant source of future revenue as the company’s COVID-19 business becomes less dominant.
The results also arrive during renewed debate about mRNA technology.
The platform has faced criticism since the COVID-19 pandemic. At the same time, researchers continue to study its potential in cancer, infectious diseases and other medical fields.
Cancer treatment presents a different use for mRNA.
A preventive infectious-disease vaccine prepares the immune system to recognize a future threat. A personalized cancer vaccine aims to help the immune system recognize specific features of a patient’s existing cancer.
That distinction could become important for the future of mRNA medicine.
The technology still faces practical limits. Manufacturing speed, treatment costs, patient selection and long-term effectiveness all require further study.
Even so, the latest melanoma result represents a major clinical milestone.
For patients with high-risk melanoma, the key issue is whether the treatment can reduce the chance of recurrence and distant spread after surgery.
The Phase 3 results indicate that the combination of a personalized vaccine and Keytruda can achieve those goals.
The next stage will depend on the complete data, regulatory review and the ability to manufacture personalized treatments on a larger scale.
