A large melanoma trial found fewer recurrences with a personalized vaccine plus Keytruda. The companies are now testing where else the approach might help.
Merck and Moderna have a promising result in melanoma, but the next question is how far it can travel. Their personalized mRNA cancer vaccine, given with Merck’s Keytruda after surgery, significantly delayed cancer recurrence and the development of metastatic disease in a large Phase 3 trial. The companies say they are preparing to seek approval. That result makes the treatment a notable advance for some people with melanoma; it does not yet establish that the same approach will work in other cancers or at other stages.
Gary Keblish, a public school teacher diagnosed with melanoma in 2019, joined an early trial after surgery to remove his tumor. At the STAT Summit in Boston, he described the experience as physically and emotionally turbulent, comparing it to a ride on the Magic School Bus. He remains a teacher. His experience gives a human face to the research, though one participant’s outcome can’t show how well a treatment works across a wider group.
The companies’ Phase 3 findings provide broader evidence. In August, they reported that the combination significantly delayed both recurrence and the spread of cancer in melanoma patients whose visible tumors had been surgically removed. The article does not provide the size of the benefit or the trial’s full results, so the finding shouldn’t be read as proof that the vaccine prevents recurrence in every patient. The results also concern treatment alongside Keytruda, not the vaccine on its own.
Why the combination is being tested
Intismeran autogene is designed around the mutations in an individual patient’s tumor. An algorithm selects as many as 34 mutant proteins, which the vaccine presents to the immune system as signals to recognize. Keytruda, an immunotherapy that has been studied in thousands of trials over 15 years, is intended to help the immune response act against cancer. The two treatments therefore play different roles: the vaccine supplies targets, while Keytruda helps strengthen the immune system’s response.
That logic doesn’t guarantee success. Tumors differ in how many mutations they carry and how readily the immune system can identify and attack them. Merck research chief Dean Li described some tumors as “hot,” where Keytruda has tended to work better, and others as “cold,” where it has been less effective. He said the companies have detailed experience with settings where checkpoint inhibitors work, nearly work, or fail. That knowledge is shaping which cancers they test next.
So far, the companies have concentrated on situations resembling the melanoma trial: Keytruda is already useful, and surgery has removed visible disease. They are running adjuvant studies in lung, kidney, and bladder cancers. Adjuvant treatment is given after a main treatment such as surgery, when the aim is to reduce the chance that cancer will return.
Where the evidence could expand
Merck and Moderna are also considering settings where Keytruda has not succeeded but another kind of immunotherapy has, and the use of the vaccine alone in very early-stage tumors. Moderna President Stephen Hoge described earlier intervention as a way to try to intercept cancer before it is diagnosed at a later stage. That possibility remains a research question; the companies have not shown that the vaccine can prevent advanced disease in people with early tumors.
Small studies in adjuvant pancreatic and gastric cancer are underway. Li also raised testing the vaccine in people whose metastatic tumors have already shrunk after other treatments. These approaches would extend the treatment into groups with different disease patterns and prior care. Results in melanoma can’t establish whether it will help in these settings, and smaller studies will need to be followed by larger trials before they can answer that.
The companies have not prioritized cold or metastatic tumors as their main next targets, Li said. He added that positive results from other research could prompt them to change course quickly. That comment reflects a strategy based on the pair’s experience with Keytruda; it is not evidence that the vaccine will work across tumor types.
Improving the personalized design
The selection algorithm is another part of the work still being refined. It must identify which tumor mutations are most useful to show the immune system, and the current process is imperfect. By studying immune responses among participants, Merck and Moderna hope to improve the software’s ability to choose targets. Hoge said the companies now have information from several thousand people in their Phase 3 program and are looking to analyze it. The article does not specify what changes that analysis may lead to, or when.
For patients and families, the practical message is measured: the combination has encouraging Phase 3 evidence in a particular melanoma setting, and research is beginning to test other uses. Anyone weighing treatment options can ask their oncology team how the trial results apply to their situation and whether a relevant clinical study is available. The central question now is whether the benefit seen after melanoma surgery can be reproduced in other cancers and patient groups.
