Merck and Moderna vaccine cuts melanoma recurrence risk by 42% in Phase 3 trial

Key Facts

The personalized intismeran autogene vaccine, when added to KEYTRUDA, cut the risk of recurrence or death by 42% in patients with completely resected melanoma, compared with KEYTRUDA alone, according to results from the Phase 3 INTerpath-001 trial announced by Merck. The finding came in a prespecified interim analysis after a median follow-up of 24.6 months. The trial also showed a statistically significant reduction in the risk of distant metastasis or death, supporting the combination therapy's results on two endpoints linked to disease recurrence and spread. But overall survival data are not yet mature, and the study is continuing to follow participants to assess them. Merck said detailed results would be presented at the presidential symposium of the 2026 ESMO Congress.

In the interim analysis, two-year recurrence-free survival was 82.2% among patients who received the vaccine with KEYTRUDA, versus 70.0% among those who received KEYTRUDA alone. On the distant metastasis-free survival measure, the combination therapy recorded 88.5% at two years, compared with 80.2% in the control group. Merck estimated a 42% reduction in the risk of recurrence or death, with a hazard ratio of 0.58, a 95% confidence interval between 0.45 and 0.75, and a p-value below 0.001. The risk of distant metastasis or death also fell 38%, with a hazard ratio of 0.62, a 95% confidence interval between 0.45 and 0.85, and a p-value of 0.002. These measures support the company's description of the differences as statistically significant, but do not yet establish the treatment's effect on overall survival.

INTerpath-001 enrolled 1,137 patients, randomly assigning them in a 2:1 ratio between the combination therapy and a group given a placebo with KEYTRUDA. The study targeted high-risk cutaneous melanoma in stages IIB to IV after complete surgical resection. Intismeran autogene is designed for each patient based on mutations specific to their tumor, then given alongside KEYTRUDA after surgery. The approach aims to train the immune system to recognize new antigens associated with the tumor. According to the Associated Press, the treatment consists of 9 doses given 3 weeks apart, while the process from tumor gene analysis to preparing a patient's formula can take about 6 weeks or more.

Safety data showed treatment-related adverse events in 95.8% of patients receiving intismeran with KEYTRUDA, versus 90.0% among those receiving KEYTRUDA alone. Grade 3 to 5 events were recorded in 14.2% of the combination group, compared with 13.4% in the control group. The company did not report mature overall survival data in the results presented here, and said the study is continuing to assess this measure and other key endpoints. Merck added that the two companies are in discussions with regulators about the data. The Associated Press also said longer-term follow-up of participants is ongoing.

Merck shares fell about 1.8% at the close on October 22, after the detailed results were published, according to Reuters. The agency said some analysts saw the data as potentially raising questions among investors about how far the technology could be extended to other types of cancer, although the trial tested surgically resected melanoma. Moderna shares also closed down more than 17% that day after the results were leaked, after having risen to nearly four times their level by Wednesday's close since the trial's success was announced in August without details being published. Moderna's chief executive said the vaccine's ability to create tumor-directed T cells “could have a profound clinical impact,” citing the durability of the effect in a Phase 2 trial. MRK shares closed at $145.27 on October 23, according to EL7 data; this value alone does not establish the stock's movement on October 26.

Merck had announced on October 13 that INTerpath-001 data would be presented at the presidential symposium of the ESMO Congress, held in Madrid from October 23 to 27, 2026. On next steps, Reuters said the two companies are preparing to file for U.S. approval and expect to launch the vaccine in 2027, according to Moderna's chief executive. The companies continue to engage with regulators, according to Merck, while the study continues to assess overall survival and longer-term outcomes. Merck is scheduled to hold an investor event on oncology on October 26 at 7:30 p.m. Central European Time, with an online broadcast. The efficacy of the approach in other cancers was the subject of questions Reuters attributed to some analysts, and was not an outcome tested by INTerpath-001.