Moderna’s mRNA cancer vaccine works even better than thought

The personalized shot gives a standard melanoma treatment a huge boost.
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Adding Moderna’s in-development cancer vaccine to a standard treatment for melanoma dramatically reduces cancer survivors’ risk of death or recurrence, according to newly shared trial data.

The challenge: To treat melanoma — the deadliest type of skin cancer — doctors typically start by surgically removing as much of the cancer as possible. They might then administer another treatment, such as chemo or radiation therapy, to kill any cancer cells they missed.

Even if a person is cancer-free after this, there’s always a chance of the melanoma coming back, and certain types are considered high-risk for recurrence, including ones that are particularly thick or that had metastasized (spread to other parts of the body) prior to treatment. 

“This is a pretty significant improvement, a pretty dramatic improvement over standard of care.”

Stephen Hoge

The cancer vaccine: Moderna and pharma giant Merck are developing an mRNA-based cancer vaccine, mRNA-4157 (V940), for people who’ve had high-risk melanomas removed.

The vaccine works by instructing the body to make up to 34 “neoantigens.” These are proteins found only on the cancer cells, and Moderna personalizes the vaccine for each recipient so that it carries instructions for the neoantigens on their cancer cells.

The idea behind the vaccine is that, by prompting the body to make these proteins, it can prepare the immune system to quickly identify and attack any new cancer cells bearing them, preventing recurrence. 

What’s new? In the ongoing phase 2b KEYNOTE-942 study, Moderna and Merck are comparing the cancer vaccine’s ability to prevent melanoma recurrence or death when combined with Keytruda, Merck’s FDA-approved cancer treatment, to Keytruda alone.

In 2022, they reported that the combo therapy reduced high-risk patients’ risk of recurrence or death by 44% compared to only Keytruda in the two years after treatment.

They’ve now announced that people who received both therapies were 49% less likely to experience recurrence or death a median of three years after treatment compared to people in the Keytruda-only group. They were also 62% less likely to experience distant metastasis or death.

“The durability of the responses is really strong — they’re essentially rock solid through this time,” Moderna President Stephen Hoge told Reuters. “This is a pretty significant improvement, a pretty dramatic improvement over standard of care with just Keytruda alone.”

“We think that in some countries the product could be launched under accelerated approval by 2025.”

Stephane Bancel

Looking ahead: The KEYNOTE-942 study is relatively small, with just 157 participants, but Moderna and Merck have already launched a phase 3 trial for the combination cancer therapy that will include more than 1,000 people with high-risk melanoma.

The companies are also looking beyond melanoma, launching a phase 3 trial testing the cancer vaccine in people with non-small cell lung cancer — and if these trials go well, it might not be long before the personalized therapy reaches patients.

“We think that in some countries the product could be launched under accelerated approval by 2025,” Moderna CEO Stephane Bancel told AFP.

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