Cancer vaccines poised to unlock ‘new treatment paradigm’ with Merck/Moderna data

CHICAGO, June 5 (Reuters) ̵[ads1]1; Addition of an experimental mRNA-based vaccine from Moderna Inc ( MRNA.O ) and Merck & Co ( MRK.N ) cut the risk of the deadliest skin cancer spreading by 65% ​​over treatment with an immunotherapy alone in a mid-phase trial, the companies reported Monday.

With these and earlier data, Moderna is considering seeking 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.

“Some of the remaining uncertainty seems to dissipate on that potential (option),” Moderna president Stephen Hoge said.

The data followed earlier promising data from the study showing that the customized 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 came to prominence during the COVID-19 pandemic, could be used to assemble personalized vaccines that train the immune system to attack the specific type of cancer cells in a patient’s tumors.

Scientists have been chasing the dream of vaccines to treat cancer for decades with few successes. Experts say mRNA vaccines, which can be produced in as little as eight weeks, along with drugs that boost the immune system could lead to a new generation of cancer treatments.

The hope is “a whole new cancer treatment paradigm that will be better tolerated and unique to individual patients’ tumors,” said Dr. Jane Healy, a manager who oversees early cancer treatment development at Merck.

Moderna said during its investor call that it was starting a phase 3 confirmatory study, which it hoped 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 ( PFE.N ) COVID vaccine partner BioNTech SE ( 22UAy.DE ) and Gritstone Bio Inc ( GRTS.O ) are taking similar approaches using mRNA technology.

The vaccines are all directed against neoantigens, new mutations that are only found on tumors. Targeting these unique proteins allows the immune system to kill cancer cells while leaving healthy tissue unharmed.

The trick is to determine which of many mutations is driving the cancer.

To achieve this, tumors are removed and their genetic makeup mapped using next-generation DNA sequencing. Companies use artificial intelligence to predict which mutations will be the most effective targets. These are used to build an individualized vaccine that only targets mutations in the patient’s tumor.

During this process, patients typically receive an immunotherapy such as Keytruda or Roche’s ( ROG.S ) Tecentriq, which blocks a mechanism that cancer uses to hide from the immune system.

‘A STARTING POINT’

Long before COVID, companies had looked to messenger RNA (mRNA) technology, which carries instructions for cells to make specific proteins, as a tool to deliver a cancer vaccine.

Merck and Moderna have collaborated since 2016. Researchers at the Memorial Sloan Kettering Cancer Center (MSK) in New York began collaborating with the German BioNTech in 2017.

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

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

Balachandran’s team studied the rare long-term survivors and found that an immune system component called T cells in these individuals was able to recognize mutations derived from the cancer, raising the possibility of a targeted vaccine.

In a small ongoing trial testing a custom-made BioNTech vaccine plus Roche’s Tecentriq, half of the 16 pancreatic cancer patients had an immune response, and none showed signs of relapse after 18 months, according to data published last month in Nature.

Gritstone Bio is taking a different tack, combining two types of customized vaccines in hopes of treating patients with metastatic colon cancer, another cancer that has largely failed to respond to immunotherapy.

The approach first primes the immune system with an older technology called a chimpanzee adenovirus vaccine that targets patients’ tumors. It is followed by a personalized self-boosting mRNA vaccine, which includes an enzyme that makes extra copies of the antigens, reducing the required dose.

Gritstone expects data from a later study testing its dual vaccine therapy in the first quarter of 2024.

“Based on everything we’ve shown and published, we’re very excited,” said Gritstone CEO Andrew Allen.

Merck and Moderna are planning a larger phase 3 study in melanoma and are also testing the combination in lung cancer.

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

Reporting by Julie Steenhuysen and Patrick Wingrove; Editing by Caroline Humer, Bill Berkrot and Sonali Paul

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