Moderna and Merck's melanoma vaccine cut recurrence or death by 42%, and Moderna stock fell 17.6%

Moderna and Merck’s personalized mRNA melanoma vaccine cut the risk of recurrence or death by 42% in a Phase 3 trial. The vaccine, intismeran autogene, was added to Keytruda after surgery. The companies released the INTerpath-001 data on Oct 22, two days early, after the results leaked. Moderna stock closed down 17.6% that day. Georgina Long of Melanoma Institute Australia presented the full results at the ESMO Presidential Symposium in Madrid on Oct 24.

What the trial showed

INTerpath-001 enrolled 1,137 patients with stage IIB to IV melanoma that surgeons had fully removed. Patients were randomized 2 to 1 to the vaccine plus Keytruda or to placebo plus Keytruda, for about a year. The trial is registered as NCT05933577.

The primary endpoint is recurrence free survival (RFS), the time until the cancer returns anywhere or the patient dies. Median follow up was 24.6 months. The hazard ratio (HR) was 0.58 (95% CI 0.45 to 0.75, p<0.001), per the companies’ Oct 22 release. At two years, 82.2% of patients on the combination were alive and recurrence free, against 70.0% on Keytruda alone. That is a gap of 12.2 points.

The key secondary endpoint is distant metastasis free survival (DMFS), which tracks spread to other organs. The HR was 0.62 (95% CI 0.45 to 0.85, p=0.002). At two years, 88.5% were free of distant spread or death, against 80.2%.

The benefit showed up late. In the first six months, the two arms were even (HR 0.99). After six months, once the nine vaccine doses were done, the HR for recurrence or death was 0.42 in a prespecified sensitivity analysis. Among patients who got at least one planned dose, the RFS HR was 0.51, a 49% cut, per Moderna’s Oct 24 recap.

What the ESMO presentation added

Overall survival is not mature. The HR was 0.77 (95% CI 0.45 to 1.31, p=0.33), and it did not meet the prespecified significance boundary, CancerNetwork reported from the Oct 24 talk. Follow up for survival continues. Data cutoff was June 30, 2026.

The cancer came back, or the patient died, in 18.0% of the combination arm and 29.2% of the Keytruda arm. Moderna said it manufactured a personal vaccine for more than 99% of patients randomized to get one. The median time to the first vaccine dose was 64 days, CancerNetwork reported.

Side effects tied to treatment hit 95.8% of patients on the combination and 90.0% on Keytruda alone. Severe ones (grade 3 to 5) were 14.2% and 13.4%. The most common were fever (52.2%), injection site pain (51.0%) and fatigue (38.5%). Side effects led 14.0% of combination patients to stop a study drug, against 8.7%.

How the data came out

The companies announced in August that the trial met both endpoints at an interim analysis, with no numbers. The full data were set for the ESMO Presidential Symposium on Oct 24. On Oct 22, an oncology news site posted some of the data ahead of the embargo, and ESMO confirmed the breach to Fierce Biotech. Merck and Moderna then put out the full release at 1:59 PM CT.

The stock move

Moderna (MRNA) closed at $245.81 on Oct 21. On Oct 22 it fell as low as $180.80, down 26.4%, and closed at $202.63, down 17.6%. On Oct 23 it closed at $200.10, down another 1.2%, per Yahoo Finance daily prices read at 5:55 PM CT. Merck (MRK) closed down 1.8% on Oct 22 and 1.3% on Oct 23, at $145.27. Markets were closed for the weekend when the full data came out.

Bloomberg reported on Oct 23 that Moderna shares remain well above their level before the August announcement.

Why doctors and investors read it differently

Oncologists decide on absolute benefit, a physician told Guggenheim analysts, per Fierce Biotech. Here, 12 more patients out of every 100 were recurrence free at two years, with severe side effects close to Keytruda alone. Michael Postow of Memorial Sloan Kettering, a trial investigator, told Bloomberg he was impressed and expects the benefit to grow with time. Sekwon Jang of Inova Schar Cancer Institute told Bloomberg he expects more of his patients to choose the combination if it is approved.

Investors compared it with the Phase 2b trial, KEYNOTE-942. At five years, that smaller study cut recurrence or death by 49% (HR 0.51). It cut distant metastasis or death by 59% (HR 0.41), per the companies’ ASCO 2026 release. The Phase 3 DMFS result of 38% came in below that. Analysts had expected an RFS hazard ratio as low as 0.5, Fierce Biotech reported. It said the DMFS result fell short of what Phase 2 set up.

Bloomberg reported that investors had priced the vaccine as the start of a wider Moderna cancer business, in lung, bladder and other cancers. It quoted RBC Capital Markets analyst Trung Huynh: “While approval seems likely, commercial success is far less certain.” Price for the vaccine: MISSING. Neither company has said what it will charge.

What comes next

Merck holds an oncology investor event on Oct 26 at 1:30 PM CT. The results are accepted for publication in The New England Journal of Medicine, and the paper is not out yet.

On regulators, the companies say they “are engaging with regulatory authorities.” FDA filing date: MISSING. Moderna’s Oct 24 recap lists “the potential for approval of intismeran in 2027” among its forward looking statements. The registry lists an estimated primary completion date of Oct 26, 2029.

The program runs nine Phase 2 and Phase 3 trials, including three Phase 3 trials in non small cell lung cancer, Moderna said.

Why it matters: The companies call this the first positive Phase 3 result for an mRNA cancer therapy. Survival data, the filing date and the price now decide how many patients get it after melanoma surgery.