A personalized cancer vaccine has taken an important step forward. In a large Phase 3 clinical trial, adding an experimental mRNA cancer vaccine to an established immunotherapy helped more patients with high-risk melanoma remain free of cancer recurrence after surgery.
For the Cancer Research Institute (CRI), these findings reflect progress in two fields of immunology that we have been deeply committed to and helped advance for decades: cancer vaccines and immune checkpoint therapies.
“It’s 35 years of working on basic immunology and biology, developing ways in preclinical models, testing in patients,” said Elizabeth Jaffee, MD, of Johns Hopkins and Associate Director of CRI’s Scientific Advisory Council. “Thirty-five years of progress to get to where we want to be, not seeing what we really wanted to see: some real clinical outcomes that are durable, and all of a sudden we’re there.”
In 2001, CRI and the Ludwig Institute for Cancer Research established the Cancer Vaccine Collaborative, an international effort to develop and test therapeutic cancer vaccines. Its early clinical studies included vaccines targeting NY-ESO-1, a protein found in several cancer types, including melanoma and ovarian cancer. Researchers explored how to generate stronger immune responses and which additional ingredients could help those responses last longer.
Meanwhile, CRI’s support of pioneering checkpoint research, including work in the laboratory of CRI’s Scientific Advisory Council Director and Nobel Laureate James P. Allison, PhD, helped establish the scientific principles behind treatments that release the immune system’s natural brakes.
Detailed findings presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid now show the size of that benefit, along with important questions that remain.
The vaccine, called intismeran autogene, is designed using genetic information from each patient’s tumor to help the immune system recognize cancer cells. It is given alongside pembrolizumab (Keytruda®), an immunotherapy that helps immune cells attack cancer.
What Did the Phase 3 Trial Find?
The INTerpath-001 trial enrolled 1,137 patients with high-risk melanoma whose tumors had been completely removed by surgery. Patients received either the personalized vaccine plus Keytruda or Keytruda alone, with the goal of preventing cancer from returning.
After a median follow-up of 24.6 months, the results showed:
- Lower risk of recurrence: Adding the vaccine reduced the risk of cancer returning or death by 42% compared with Keytruda alone. At two years, approximately 82% of patients receiving the combination were alive without their cancer returning, compared with 70% receiving Keytruda alone.
- Lower risk of cancer spreading: The combination also reduced the risk of distant recurrence or death by 38%. At two years, approximately 89% of patients receiving the combination were alive without their cancer spreading to another part of the body, compared with 80% receiving Keytruda alone.
What Do These Results Mean?
These findings provide encouraging evidence that personalized cancer vaccines can improve outcomes when added to an existing immunotherapy. Building on promising findings from an earlier, smaller trial, this larger study provides stronger evidence that the combination can help prevent melanoma recurrence.
There are important limitations. We do not yet know whether the treatment helps patients live longer. Overall survival data remain immature, and longer follow-up is needed.
Safety matters, too. Fever, injection-site pain, and fatigue were more common among patients receiving the vaccine. Severe treatment-related side effects occurred in approximately 14% of patients in both groups.
How Can Cancer Vaccines Help More Patients?
The melanoma results illustrate the promise of combining cancer vaccines with checkpoint immunotherapy. But generating an immune response is only part of the challenge. The next step is understanding how to make those responses more effective and durable, particularly in cancers that have been resistant to immunotherapy.
A separate Phase 2 trial testing a personalized mRNA vaccine without checkpoint immunotherapy in colorectal cancer was discontinued earlier this year. While the studies differed in important ways, the contrasting outcomes underscore how much remains to be learned about where and how cancer vaccines work best.
Addressing these challenges requires advances on several fronts. Scientists need to identify cancer targets that trigger effective immune responses, improve how vaccines reach and activate immune cells, and understand why some tumors remain resistant even when an immune response is generated.
CRI is supporting research across these areas. By combining immunology with data science, researchers are uncovering potential vaccine targets, including those shared across patients and cancer types. Others are developing technologies to deliver mRNA more precisely to immune cells or investigating why vaccine-induced immune responses succeed in some patients but weaken or fail in others. Together, these efforts could help make vaccines more effective and extend their potential beyond cancers that already respond well to immunotherapy.
Equally important is translating these discoveries into treatments for patients. CRI CLIP Investigator and Associate Director of the Scientific Advisory Council Nina Bhardwaj, MD, PhD, is investigating vaccine strategies for blood and bladder cancers, building on CRI’s early Cancer Vaccine Collaborative and ongoing research. Her CRI-supported studies are exploring whether vaccines can stimulate effective immune responses in patients with active cancer and whether vaccines targeting changes shared by many patients could offer alternatives to fully personalized approaches.
Looking Ahead
Intismeran remains investigational and has not yet been approved for routine use. Merck and Moderna are engaging with regulatory authorities while continuing to follow patients in the trial.
Researchers are also testing the approach in other cancers, including lung, kidney, and bladder cancer, to understand where personalized vaccines may offer the greatest benefit.
The INTerpath-001 results mark an important milestone, but they are also a reminder of how much work lies ahead. For CRI, the priority remains advancing the science that can turn promising immune responses into lasting clinical benefits, and ultimately extend those benefits to more patients and more types of cancer.
Sources
Phase 3 INTerpath-001 results presented at ESMO 2026
Merck and Moderna, October 22, 2026
BioNTech Provides Update on Phase 2 Clinical Trial of Autogene Cevumeran in Resected Colorectal Cancer
BioNTech, August 28, 2026
A New Milestone for Cancer Vaccines — Decades in the Making.
Cancer Research Institute, August 27, 2026
