Moderna and Merck melanoma vaccine data come out early after a leak

What happened

Merck and Moderna published the detailed Phase 3 results of their personalized melanoma vaccine on Thursday 22 October, after part of the data surfaced before a Saturday medical meeting. ^{[1, 3, 4]}

The trial, INTerpath-001, gave 1,137 high-risk patients whose melanoma had been removed by surgery either the vaccine, intismeran autogene, with Merck's Keytruda, or a placebo with Keytruda. After a median follow-up of 24.6 months, the combination cut the risk of the cancer returning or death by 42 percent, the companies said. It cut the risk of distant spread or death by 38 percent. ^[1]

Why it matters

Merck's research chief, Dean Li, said it is the first Phase 3 study to show a clinically meaningful improvement over Keytruda alone in melanoma removed by surgery. After two years, 82.2 percent of patients on the combination were alive without recurrence, against 70.0 percent on Keytruda alone, the companies reported. Free of distant spread at two years were 88.5 percent and 80.2 percent. ^[1]

How the figures came out

The European Society for Medical Oncology, ESMO, had held the data for a presentation at its congress in Madrid on Saturday 24 October. 'As the data are now publicly available, ESMO has released the abstract and has lifted the embargo on the full dataset,' the society told reporters on Thursday evening, the Boston Globe reported. ^{[2, 4]}

Accounts of the leak differ. BioPharma Dive reported that screenshots of the findings were posted on social media; STAT, in the copy the Globe republished, wrote that an oncology news website published some of the data. Both reports carry the same 42 and 38 percent figures as the companies. ^{[1, 3, 4, 5]}

What the details show

The benefit did not show at first. In the first six months the two groups did about equally, a hazard ratio, the trial's measure of relative risk, of 0.99. From six months on, a pre-specified analysis showed the risk of recurrence or death 58 percent lower with the vaccine, the companies said. ^[1]

The distant spread figure is smaller than the 59 percent reduction an earlier, smaller study showed, the Globe noted. Overall survival data are not yet mature, and the companies said a favorable trend has been observed. Severe treatment-related side effects, grade 3 to 5, occurred in 14.2 percent of patients on the combination and 13.4 percent on Keytruda alone. ^{[1, 4]}

What settles it next

Georgina Long of Melanoma Institute Australia, the study's lead investigator, presents the results at 10:30 a.m. Eastern on Saturday 24 October, and Moderna holds an investor webcast at 1:00 p.m. Eastern. The results have been accepted for publication in The New England Journal of Medicine. ^{[1, 2]}

The release names engagement with regulatory authorities among its forward-looking statements and gives no filing date. Neither company had filed a current report with the SEC on the results by Friday 23 October, according to their EDGAR records. ^{[1, 6, 7]}

Who it reaches

Moderna (MRNA) is direct: it develops intismeran jointly with Merck, and each dose is designed and made from a patient's own tumor sample. Merck (MRK) is direct: it co-develops intismeran, and the trial paired it with Keytruda, Merck's own immunotherapy and the comparison treatment. ^[1]