Moderna-Merck melanoma vaccine cuts death or recurrence 42%

By Olivia Hart

A Phase 3 trial in more than 1,100 patients with melanoma found that adding a personalized mRNA cancer vaccine to Keytruda reduced the combined risk of death or recurrence by 42%, Moderna and Merck reported Thursday.

Full data are scheduled for Saturday at the European Society for Medical Oncology meeting in Madrid; Thursday’s release set out the headline endpoints and the two-year outcome.

The trial in three numbers

• Death or recurrence: 42% lower risk with the vaccine combination than with Keytruda alone.
• Cancer spread: 38% lower reported risk with the combination.
• Two years: 82.2% of combination patients remained cancer-free, compared with 70% on Keytruda alone.

That 12.2-percentage-point gap means about 12 more patients per 100 in the combination group remained cancer-free at two years. The trial compared the vaccine-plus-Keytruda regimen with Keytruda alone.

Intismeran autogene, the investigational vaccine’s name, is built around mutations unique to each patient’s tumor, the companies said. The melanoma trial therefore tested an individualized cancer vaccine added to Keytruda, rather than a vaccine alone.

What does this change for melanoma care?

Intismeran autogene has no approval. Moderna and Merck are preparing to file for U.S. approval, and Moderna’s chief executive expects a launch in 2027. That date represents a company forecast, not a regulatory decision.

For dermatologists and oncology teams, the immediate change is a late-stage candidate, not a newly approved treatment option. Regulatory approvals already cover Keytruda for 19 cancer types; they do not yet cover intismeran autogene.

The companies are also testing the combination in kidney, bladder and lung cancer. Investors will watch whether the melanoma result travels to those tumor types, which the melanoma study did not address.

The market reaction

The 42% result landed close to what Wall Street expected: analysts had hoped for a reduction of 40% or more. One RBC analyst said melanoma “was supposed to be the best case” while raising concerns about how broadly the vaccine would work in other cancers.

Moderna announced the trial’s success in August without releasing the data, and its stock has risen more than 300% since. When the results leaked Thursday, Moderna closed more than 17% lower; Merck fell about 1.8%, a much smaller move.

Keytruda remains central to Merck’s commercial position. On its latest earnings call, Merck reported quarterly Keytruda sales of $8.4 billion, up 4%, and said U.S. growth should slow as the drug reaches peak use in key indications.

A vaccine that works alongside Keytruda could help support the franchise in that setting. Merck has also identified $70 billion in commercial opportunity across more than 20 new products.

Merck’s chief executive described the coming Keytruda patent loss as “more of a hill than a cliff.”

As of Oct. 21, Merck traded at $147, compared with a 52-week high of $157 and a stated price target of $159. Merck shares had gained 28% over the previous six months.

For now, Merck stock reflects both the strong melanoma data and the questions that follow. No approval exists yet for the vaccine combination.

Clinicians should wait for the full Madrid presentation and the U.S. filing before drawing wider conclusions about the vaccine’s role. The next checkpoints are regulatory review and evidence of benefit in kidney, bladder and lung cancer; the 42% and 38% reductions remain confined to the reported melanoma trial results.