Moderna Cancer Vaccine Cuts Cancer Recurrence Risk by 42%... Shares Plunge After Results Leak

MSD Releases Phase 3 Melanoma Results
Smaller Reduction Than in Phase 2 (49%)

A personalized messenger RNA (mRNA) cancer vaccine being jointly developed by U.S.-based Moderna and Merck (MSD) reduced the risk of recurrence or death by 42% compared with Keytruda alone in high-risk melanoma patients whose tumors had been surgically removed. This is the first Phase 3 trial to show that the vaccine reduced both recurrence and metastasis compared with standard treatment with Keytruda in patients with completely resected melanoma. However, the data leaked before the official announcement, and the results were lower than those of an earlier Phase 2 trial, sending Moderna shares down more than 17% in a single day.

On October 22 local time, MSD and Moderna issued a press release detailing the Phase 3 results for the combination of intismeran autogene (development code: mRNA-4157/V940) and Keytruda. The trial included 1,137 patients with Stage IIB to Stage IV melanoma whose tumors had been completely resected. Patients were assigned in a 2:1 ratio to receive either intismeran and Keytruda or a placebo and Keytruda. Intismeran was administered every three weeks for up to nine doses, while Keytruda was administered every six weeks for up to nine doses (approximately one year).

Moderna corporate logo image. Moderna

An analysis of patients followed for approximately two years found that the risk of recurrence or death in the combination group was 42% lower than in the Keytruda-only group. The risk of the cancer spreading to other organs or the patient dying was reduced by 38%. Two years after starting treatment, 82.2% of patients in the combination group were alive without recurrence, compared with 70.0% of those in the Keytruda-only group. The proportions whose cancer had not spread to other organs were 88.5% and 80.2%, respectively.

The benefit increased after patients completed the vaccination course. During the first six months, when vaccinations were being administered, there was no difference between the groups in the risk of recurrence or death. Looking only at the period after six months, the combination group had a 58% lower risk of recurrence or death and a 50% lower risk of the cancer spreading to other organs or death. When patients who had not received even one dose of the vaccine or placebo were excluded from the analysis, the risk of recurrence or death was reduced by 49%.

It is too early to determine whether the treatment actually extends survival. However, MSD and Moderna said they had observed a trend toward longer survival in the combination group. The proportion of patients who experienced serious side effects was similar in the combination and monotherapy groups, at 14.2% and 13.4%, respectively. The companies are consulting with regulators based on these results. The findings will be officially presented at the European Society for Medical Oncology (ESMO 2026), which opened in Madrid, Spain, on October 23 local time. They will also be published in the New England Journal of Medicine (NEJM).

The results spread through the market about two and a half hours before the official announcement. On October 22 local time, medical news outlet Oncology Central posted the results, then quickly removed them. Moderna shares fell as much as 26% during the trading session before closing down 17.57%. This was the largest intraday decline on record. MSD shares also fell 1.76%.

The market appears to have reacted negatively to the fact that the reduction in the risk of recurrence or death in Phase 3 was smaller than in the earlier Phase 2 trial. In the five-year follow-up results from the Phase 2 KEYNOTE-942 trial, presented at this year's annual meeting of the American Society of Clinical Oncology (ASCO), the combination therapy reduced the risk of recurrence or death by 49%—a reduction 7 percentage points greater than the 42% reported in Phase 3. The Phase 2 trial included 157 patients with Stage III to Stage IV disease, while the Phase 3 trial included 1,137 patients, including patients with Stage IIB disease, which is less advanced. In Phase 2, patients and medical staff knew which drug was being used, whereas the Phase 3 trial was blinded using a placebo.

Another factor is believed to be that expectations had already been priced into the stock. Moderna shares posted their largest-ever single-day gain on August 19, 2026, when the company announced that the Phase 3 trial had met its goals. The shares then rose nearly fourfold through October 21. As of October 21, they were up approximately 700% this year, and the company's market capitalization had reached approximately $98 billion (about KRW 130 trillion).

Intismeran is a personalized treatment made as a different product for each patient. First, the patient's tumor DNA is compared with their normal DNA to identify mutated proteins (neoantigens) found only in that patient's cancer cells. mRNA containing up to 34 neoantigens is then produced, packaged in lipid nanoparticles (LNPs), and administered.

The treatment works by prompting the body to produce neoantigens, which immune cells recognize as targets and use to attack cancer cells. Moderna signed an agreement with MSD in 2016 to jointly develop personalized cancer vaccines. In September 2022, MSD exercised an option under the agreement, securing the rights to jointly develop and commercialize intismeran. The following month, MSD paid Moderna an option exercise fee of $250 million (approximately KRW 331.1 billion).

This content was produced with the assistance of AI translation services.