Adding an experimental mRNA-based vaccine from Moderna and Merck & Co has cut the risk that the deadliest skin cancer will spread by 65% ​​in a mid-stage trial with just one immunotherapy, the companies reported Monday.

With this and earlier data, Moderna is looking for faster approval from regulators for the treatment, the company told investors after presenting the results at the American Society of Clinical Oncology meeting in Chicago.

“There’s some residual uncertainty going away on that potential (option),” said Stephen Hogg, Moderna’s president.

Promising data from an earlier trial showing the optimized mRNA vaccine given in combination with Merck’s Keytruda reduced the risk of death or recurrence of melanoma by 44% compared to Keytruda alone.

The findings add to a growing body of evidence suggesting that mRNA technology, which rose to prominence during the COVID-19 pandemic, could be used to assemble personalized vaccines that target the immune system with specific types in a patient’s tumor. Let’s train to attack cancer cells.

Scientists have been chasing the dream of vaccines to treat cancer for decades with some success. Experts say mRNA vaccines, which can be prepared in less than eight weeks, combined with drugs that rev up the immune system could lead to a new generation of cancer treatments.

An executive overseeing the development of early cancer treatments at Merck, Dr. “There is hope for an entirely new treatment paradigm in cancer that will be better tolerated and will be unique to individual patients’ tumours,” said Jane Healy.

Moderna said during its investor call that it was beginning a Phase 3 confirmatory study, which it expected to open in the third quarter of this year.

The Merck/Moderna collaboration is one of several combining powerful drugs that unleash the immune system to target cancer with mRNA vaccine technology. Pfizer’s COVID vaccine partners BioNTech and Gritstone Bio are taking a similar approach, using mRNA technology.

Vaccines all target neoantigens, new mutations that are present only on tumors. Targeting these unique proteins allows the immune system to kill cancer cells while sparing healthy tissue.

The trick is determining which mutations are driving the cancer.

To accomplish this, tumors are removed and their genetic makeup is mapped using next-generation DNA sequencing. Companies use artificial intelligence to predict which mutations will be the most effective targets. These are used to create a personalized vaccine by targeting only the mutations in a patient’s tumour.

During this procedure, patients typically receive an immunotherapy such as Keytruda or Roche’s Techentriq, which blocks a mechanism that cancer uses to hide from the immune system.

‘a starting point’

Long before COVID, companies were eyeing messenger RNA (mRNA) technology, which instructs cells to make specific proteins, as a vehicle to deliver cancer vaccines.

Merck and Moderna have been collaborating since 2016. Researchers at Memorial Sloan Kettering Cancer Center (MSK) in New York began working with Germany’s BioNTech in 2017.

At the time, there was already evidence that immunotherapy could work in so-called “hot” tumors, or highly mutated cancers such as melanoma. MSK’s Dr Vinod Balachandran said there was little hope that it would work in “cold” cancers with certain mutations, such as pancreatic cancer.

With standard treatment, 90% of patients with pancreatic cancer die within five years of diagnosis.

Balachandran’s team studied rare long-term survivors and found in these individuals an immune system component called T cells were able to recognize cancer-causing mutations, increasing the potential for targeted vaccines.

In a small ongoing trial of the made-to-order BioNTech vaccine plus Roche’s Techentriq, half of 16 pancreatic cancer patients mounted an immune response, and none after 18 months, according to data published last month in Nature. Shows no signs of recurrence.

Gritstone Bio is taking a different step by combining two types of optimized vaccines in hopes of treating patients with metastatic colon cancer, another cancer that has been largely unresponsive to immunotherapy.

The approach first primes the immune system with an older technique called a chimpanzee adenovirus vaccine that targets patients’ tumors. This is followed by a personalized self-amplifying mRNA vaccine, which includes an enzyme that makes extra copies of the antigen, reducing the dose needed.

Gritstone is expecting data from a later-stage trial of its dual vaccine therapy in the first quarter of 2024.

“We’re really excited based on what we’ve shown and what we’ve published,” said Andrew Allen, CEO of Gritstone.

Merck and Moderna are planning a large Phase 3 trial in melanoma and also testing its combination in lung cancer.

“We view this as a starting point,” Healy said.