Every cancer is different. So it makes sense that every cancer treatment should be different as well. Now, through innovative clinical trials, researchers are working to make cancer treatments unique – personalized to a particular patient's needs.
MUSC Hollings Cancer Center is participating in two such studies. The large international Phase 3 clinical trials – one for melanoma and one for lung cancer – are testing a new type of treatment called individualized neoantigen therapy (INT). INTs are tailor-made messenger RNA (mRNA) therapies that train the immune system to fight cancer more effectively.
"These trials bring hope by offering access to treatments that patients couldn't get otherwise," said Jennifer Kinsey, the program manager for melanoma and lung cancer trials in the Clinical Trials Office at Hollings.
While thought of as cancer vaccines, INTs differ in a key way. Unlike traditional vaccines, the therapy is not preventive. Rather, INTs are designed for patients who already have cancer, and they use a patient's own tumor to help to prevent the cancer from coming back.
A personalized approach to protecting against cancer
All patients in the trials receive pembrolizumab, better known as Keytruda, a Food and Drug Administration-approved immunotherapy that helps the immune system to attack cancer cells. Additionally, along with Keytruda, some patients are randomly selected to receive the INT mRNA-based therapy.
Keytruda has already transformed cancer care, reducing the chances of cancer returning for many patients. But, as melanoma oncologist Russell Jenkins, M.D., Ph.D., explained, the medication does not protect everyone.
"Standard treatments reduce the risk of recurrence by about 40% to 50%," he said. "That's a big improvement – but it's not a home run."
"I describe it like handing the immune system a wanted poster. The INT shows exactly what to look for so it can hunt down any stray cancer cells left after surgery."Russell Jenkins, M.D., Ph.D.
INTs are designed to boost those odds. After taking tumor tissue from each patient, researchers analyze dozens of unique mutations and encode them using mRNA technology. That then allows them to design a personalized injection that trains the immune system to recognize and attack lingering cancer cells. Thus, while Keytruda revs up the immune system, the INT therapy comes in to pinpoint its target.
"I describe it like handing the immune system a wanted poster," Jenkins said. "The INT shows exactly what to look for so it can hunt down any stray cancer cells left after surgery."
Cancer researchers have been working on mRNA technology since the early 1990s. Jenkins began enrolling patients in clinical trials using mRNA back in 2019, but it was not until the technology was adapted for creating a COVID-19 vaccine that most people heard of it.
"This technology was being pioneered for cancer before COVID," Jenkins noted. "The pandemic simply showed how nimble mRNA platforms can be. In oncology, we're now seeing that same power applied to give patients more effective, personalized treatments."
Inspiring hope – and balancing safety
In the clinical trials, all participants receive the standard Keytruda infusion every three to four weeks. They also get nine shots over a year, consisting of either the personalized INT or an inactive placebo. The studies are designed so that participants are randomly assigned to receive either the INT or a placebo, and neither they nor their doctors know which they were given. This is referred to as a double-blind study.
"It's about seeing if we can make what's already working work even better," said Sarah Mulhern, assistant director of clinical operations in the Clinical Trials Office at Hollings.
At Hollings, the melanoma trial is well underway. Interest was so high that global enrollment closed just over a year after it began.
"Before we even opened, patients were calling the clinic asking when it would be available," Kinsey said of the melanoma INT.
Patients' overwhelming interest followed promising results from an earlier Phase 2 trial: 80% of patients who received Keytruda plus the INT were cancer-free after 18 months, compared with 60% of those on Keytruda alone. That encouraging data led to the large international Phase 3 trial underway, with more than 1,000 adult patients enrolled.
With enrollment complete, it is now a waiting game while patients finish treatment and are followed up. The primary endpoint is recurrence-free survival, referring to the time until the cancer comes back or spreads, which will be measured over the first two to three years, with longer follow-up continuing out to six years.
For Jean English, who recently completed the full course of shots in the melanoma clinical trial, joining the trial meant months of appointments, coming in every three weeks for the nine shots, plus accompanying scans and lab work.
"Every time I got the vaccine, I was sick for about two days – high fever, really sore arm," she recalled. "But that made me feel like I was really getting the medicine. I decided it was worth it if it could help me or help someone else down the road."
Easing the experience, she said, was her care team: "From the check-in people to the nurses to the doctors, everybody was wonderful. I always felt like I got the best treatment. My doctor even remembered little details about my family. That really surprised me and meant a lot."
Jenkins emphasized that safety is a top priority. So far, most side effects have been mild, with patients experiencing temporary flu-like symptoms or soreness at the injection site.
And, for patients worried about being "guinea pigs," he emphasized that trial participation often means closer care, more regular monitoring and greater safety oversight. Plus, earlier trials already showed that the therapy is safe and effective.
"It doesn't really add much in terms of risk," he said. "But it does seem to add benefit."
Why clinical trials matter
At Hollings, these studies are about more than testing a new drug. They are also about giving patients access to treatments not available elsewhere.
"The investigational therapy may offer better outcomes than the current standard of care," Mulhern explained. "Every trial gives us the chance to push science forward while offering patients hope for better outcomes."
Melanoma survivor English said her experience changed the way she thinks about research.
"At first, I was scared," she said. "Looking back, I think doing the trial is a really good thing. … I'd tell other patients: Ask a lot of questions and know what you're getting into. But don't be afraid to try; a trial could help you, and it will definitely help people who come after you."
Moving cancer care into the future
If the Phase 3 trial confirms earlier results, INTs could mark a major step forward in melanoma care – and potentially for other cancers as well.
"Melanoma has often been the testing ground for new immunotherapies," Jenkins said. "Once we show it works there, the next question is whether it could work in tougher cancers like pancreatic cancer or brain tumors."
Meanwhile, Hollings continues to enroll patients in the Phase 3 trial of an INT for lung cancer. Recruitment has been slower, but it represents another chance for patients in South Carolina to access cutting-edge treatments close to home. Until then, Jenkins reminds patients that prevention matters, with offense ultimately being better than defense.
