New York: A personalised mRNA cancer vaccine being developed by Moderna and Merck has shown encouraging results in a late-stage trial when combined with Merck’s immunotherapy Keytruda (pembrolizumab) for patients with melanoma.
The Phase 3 INTerpath-001 trial met its primary goal of improving recurrence-free survival and also achieved a key secondary goal related to distant metastasis-free survival, according to the companies.
The findings suggest that adding the personalised treatment, intismeran autogene, to Keytruda may help reduce the risk of melanoma returning or spreading compared with Keytruda alone.
However, the treatment remains investigational, and the full trial data have not yet been released.
What did the Phase 3 melanoma trial find?
The INTerpath-001 trial involved 1,137 patients with completely resected stage IIB, IIC, III or IV melanoma who had not previously received systemic treatment.
Participants were randomly assigned to receive either the combination of intismeran autogene and Keytruda or Keytruda alone for approximately one year.
According to Moderna and Merck, the combination produced statistically significant and clinically meaningful improvements in both recurrence-free survival and distant metastasis-free survival.
Recurrence-free survival measures how long patients remain free of cancer returning, while distant metastasis-free survival looks at the period during which cancer does not spread to distant parts of the body.
The study will continue to evaluate other outcomes, including overall survival.
What is a personalised mRNA cancer vaccine?
Unlike conventional vaccines that are designed to prevent infections, a personalised cancer vaccine is developed using information specific to an individual patient’s tumour.
After a tumour is surgically removed, doctors can analyse its genetic mutations and identify potential neoantigens — tumour-specific markers that may help the immune system distinguish cancer cells from healthy cells.
Intismeran autogene is designed using the mutation profile of an individual patient’s tumour. The mRNA-based treatment is intended to train the immune system to recognise and attack cancer cells carrying those specific targets.
This approach is part of the growing field of precision oncology, which aims to tailor cancer treatment according to the biological characteristics of an individual’s tumour.
Keytruda combination shows potential
Keytruda is an established immunotherapy used to treat several cancers, including melanoma. It works by helping the immune system recognise and attack cancer cells.
The latest results are significant because they indicate that combining Keytruda with a treatment designed around the individual mutations of a patient’s tumour could provide additional benefits after surgery.
The companies said the safety profile of the combination was consistent with previously reported studies and that no new safety signals were identified.
However, the detailed results, including the size of the benefit and longer-term outcomes, are expected to be presented at a future medical meeting.
Why the results matter for melanoma
Melanoma is the most serious form of skin cancer and can become more difficult to treat when it spreads to other parts of the body.
For patients with high-risk melanoma who have undergone surgery, preventing the cancer from returning or spreading is an important treatment goal.
A personalised cancer vaccine could potentially add another layer of immune protection by helping the body’s immune system recognise tumour cells based on mutations specific to that patient’s cancer.
The latest Phase 3 results therefore represent an important development in the research into personalised cancer treatment.
Earlier studies provided encouraging results
The latest findings build on earlier research into intismeran autogene and Keytruda.
Five-year results from the earlier KEYNOTE-942 study showed sustained improvement in recurrence-free survival among patients who received the personalised mRNA treatment with Keytruda compared with Keytruda alone.
The earlier research also showed a reduction in the risk of distant metastasis or death, while an exploratory analysis of overall survival indicated an encouraging trend.
The treatment, however, remains investigational and has not yet been established as a standard personalised cancer vaccine treatment.
What happens next?
Moderna and Merck plan to present detailed findings from the Phase 3 study at an upcoming international medical meeting and discuss the results with regulatory authorities.
The trial is continuing to assess additional outcomes, including overall survival.
This is important because the currently announced results show improvements in recurrence-free and distant metastasis-free survival, but they do not yet establish whether the treatment helps patients live longer.
The companies are also studying intismeran autogene in other cancers as part of their broader INTerpath programme, including non-small cell lung cancer, bladder cancer and renal cell carcinoma.
What could personalised cancer vaccines mean for the future?
The latest results could strengthen interest in personalised mRNA therapies as a potential part of precision cancer treatment.
Instead of using the same vaccine design for every patient, the approach attempts to develop treatment based on the specific mutations found in an individual’s tumour.
If future studies confirm the benefits and establish a favourable long-term safety profile, personalised cancer vaccines could become an important area of research in the treatment of solid tumours.
For now, the Phase 3 results are an encouraging milestone, but detailed clinical data, longer follow-up and regulatory review will be needed to determine the treatment’s eventual role in melanoma care.