Merck and Moderna announced Wednesday that their personalized cancer vaccine helped prevent the return and spread of melanoma in a large clinical trial involving more than 1,000 patients, the companies said.
The patients had localized tumors that had been surgically removed but carried a high risk of recurrence. Moderna said it expects thousands of melanoma patients could benefit from the vaccine in the first years after approval.
Personalized cancer vaccines differ from chemotherapy, which kills healthy and cancerous cells alike, and from immunotherapy, which broadly stimulates the immune system. Instead, they train the immune system to attack the specific mutations found only in a patient's own tumor.
Dr. Ryan Sullivan, director of the Melanoma Center at the Mass General Brigham Cancer Institute, said it was a major advance for the field in general. He said the positive study brought hope, and likely future investment, that these approaches could change how cancer is treated more broadly.
Dr. Julie Gralow, chief medical officer of the American Society of Clinical Oncology, said the trial result represented a monumental leap, validating mRNA technology as a cancer treatment.
More trials target other cancers
Beyond melanoma, personalized cancer vaccines are in late-stage development for several types of tumors. Merck and Moderna have several large clinical trials under way for surgically removed non-small cell lung cancer.
They are also studying the combination in mid-stage trials involving bladder and kidney cancer patients, and in early-stage trials involving pancreatic and stomach cancer, with several trial results expected over the next year or two, Moderna president Stephen Hoge told Reuters.
Roche and BioNTech, whose mRNA technology was used in Pfizer's Covid-19 vaccines, are testing a similar treatment called autogene cevumeran in mid-stage trials involving colon and pancreatic cancer patients who have undergone surgery. Results from the colon cancer trial are expected in 2027, followed by results from the pancreatic cancer trial in 2031.
Dr. Robert Vonderheide, director of the Abramson Cancer Center at Penn Medicine and president-elect of the American Association for Cancer Research, said results from several studies were expected in the coming years and there was every reason to hope, now with this news, that many of them would be positive.
How the treatment works
The Merck and Moderna treatment, known as autogene intismerano, involves activating the immune system with up to nine doses of Merck's immunotherapy drug Keytruda, infused every six weeks, along with up to nine doses of a personalized mRNA vaccine that instructs the immune system to attack the patient's specific cancer cells.
When used alone after surgery to reduce the risk of melanoma recurrence, Keytruda is given every three to six weeks for up to a year.
In melanoma patients, Keytruda treatment can cause fatigue, diarrhea, skin rashes and inflammation of the joints and muscles, and in some cases can affect healthy organs. The companies said they had not observed new side effects with the addition of the vaccine.
The clinical trial is ongoing and the companies have not yet released full results. They will continue following volunteers to determine whether the drug extends overall survival.
Five-year data from an earlier mid-stage study, presented in June, showed the vaccine cut the risk of cancer recurrence in half and reduced the risk of spread to new areas by 59%, compared with Keytruda alone. In that trial, adding an mRNA vaccine also did not show an increase in the rate of serious side effects.
Hoge said what they saw in the mid-stage trial were the kinds of reactions people had when getting a flu shot, a Covid vaccine or any other vaccine.
Melanoma as a test case
Dr. Elizabeth Buchbinder, a melanoma specialist at the Mass General Brigham Cancer Institute, said doctors treating patients whose cancer had been surgically removed often weighed the benefits of Keytruda treatment against the risk of side effects, especially for patients with only a 20% risk of cancer recurrence.
She said the added benefit of the vaccine could change that calculation.
Buchbinder said one of the main reasons melanoma was chosen for testing in combination with Keytruda was that it is a tumor that produces many mutations, making it easier for the immune system to detect. She said many other types of cancer also produce multiple mutations, suggesting the approach could have broad applicability.
She said it remained to be seen, but that this was definitely an area poised to expand rapidly, especially with these results now being released.
