A personalized cancer vaccine developed by Merck and Moderna significantly lowered the risk that dangerous melanoma would return or spread following surgery, according to results from a major late-stage clinical trial that could represent an important advance in cancer treatment.
The companies said the findings represent the first successful Phase 3 trial involving a personalized cancer treatment based on mRNA technology.
The global study, known as INTerpath-001, included 1,137 patients who had undergone surgery for high-risk melanoma ranging from Stage IIB through Stage IV. Participants were randomly divided between those receiving the immunotherapy drug Keytruda together with the individualized cancer vaccine and those receiving Keytruda with a placebo.
Patients treated with the vaccine-Keytruda combination achieved significantly better “recurrence-free survival,” indicating that their melanoma was less likely to come back compared with patients treated with Keytruda alone.
Researchers also found a significant improvement in “distant metastasis-free survival,” which measures how long patients survive without their cancer spreading to distant areas of the body.
“These phase 3 findings represent a pivotal moment for the field of cancer research,” Stéphane Bancel, CEO of Moderna, said in the press release. “For many years, the idea of creating an mRNA treatment designed specifically for an individual patient’s cancer was aspirational. We are now helping turn that vision into a reality.”
How the Personalized Vaccine Works
Rather than functioning like conventional vaccines designed to protect people from outside viruses, the personalized mRNA treatment, known as intismeran autogene, is a therapeutic vaccine administered after cancer surgery. Its purpose is to teach the patient’s immune system to recognize and destroy cancer cells that may remain behind.
Following removal of a patient’s tumor, doctors collect samples of both the malignant tissue and healthy cells. Sophisticated algorithms then examine the genetic characteristics of the tumor and identify as many as 34 tumor-specific neoantigens that can be incorporated into a vaccine created specifically for that individual.
Dr. Murad Alam, chief of dermatology at Northwestern Medicine in Chicago, explained that melanoma can vary significantly from one patient to another, making individualized treatment particularly promising.
“They’re slightly different in every patient, which is why traditional chemotherapies often stop working or don’t work in a particular patient,” he told Fox News Digital. “This is almost individualized immunotherapy, where you’re finding specific issues in a particular patient.”
The strategy is intended to focus the immune system directly on the unique characteristics of a patient’s tumor rather than broadly attacking cells throughout the body.
“It doesn’t hit normal cells, and it hits the cancer cells very effectively because it’s not just a generic vaccine. It’s one that specifically knows the signs of your cancer and can find it,” he said.
Alam said the treatment is aimed primarily at prolonging the lives of patients who “already have a bad case of the disease.”
The vaccine is not designed to protect healthy individuals from developing melanoma, including people whose family history places them at elevated risk. It also is not intended for patients diagnosed with very small melanomas.
“This is designed for people where the melanoma has grown to the point where it’s threatening not just the local area of the skin, but their whole lives,” Alam said.
The Role of AI
Artificial intelligence plays an important part in creating the personalized vaccine, helping researchers determine which antigens should be selected to produce the strongest possible response against each patient’s cancer.
“These things are difficult, and, historically, [they] took a lot of time, and it just wouldn’t be feasible to do this for every individual patient without the power of AI,” he said. “And I’m sure that will become better and better in the future.
“Here, AI is a tool that allows you in a reasonable amount of time, with a reasonable amount of resources … to come up with a vaccine for that individual person.”
What Comes Next
Following the positive Phase 3 results, Merck and Moderna said they intend to begin discussions with regulatory agencies around the world, including the U.S. Food and Drug Administration, regarding possible regulatory submissions for the treatment.
Researchers are also preparing to investigate whether the same personalized vaccine technology can be used against other difficult cancers, including cancers of the lung, bladder and kidney.
“I think the underlying concept of targeting a particular tumor with the specific markers on that tumor is generalizable, meaning you could do this with different kinds of skin cancer or different kinds of cancer in general,” Alam agreed. “It’s very exciting.”
Despite the encouraging findings, significant questions remain. The companies described the trial results as statistically significant and clinically meaningful, but the announcement did not disclose how long participating patients remained free of cancer.
The Phase 3 findings also did not determine whether patients receiving the personalized vaccine ultimately live longer than those treated with Keytruda alone.
In addition, the recurrence-free survival findings were determined through assessments by study investigators rather than through an independent central review, according to the announcement.
The trial was limited to patients with particular stages of melanoma who had undergone surgery and had not previously received drug treatment. As a result, the findings cannot necessarily be applied to patients with other forms of cancer or melanoma at different stages.
Merck said the safety profile observed during the latest trial was consistent with previous studies and that researchers did not identify any new safety concerns.
Alam said the treatment appears to combine a “tremendous benefit [and] good side effect profile.”
He noted that traditional powerful cancer treatments can sometimes exact a significant physical price even when they successfully attack the disease.
“When you’re getting very strong cancer medications, even when they work, the toll on the patient is often terrible,” he said. “It alters their life during the course of treatment where there’s tremendous suffering.
“The nice thing about this, because it’s so targeted, it doesn’t damage many of your normal cells … so the side effects are really mild — a little fatigue, a little chills, some injection side pain.”
{Matzav.com}
