Moderna and Merck report positive Phase 3 trial results for personalized mRNA melanoma vaccine

Phase 3 clinical trial findings

Moderna and Merck announced that their experimental mRNA cancer vaccine, intismeran autogene, met its primary endpoint in the Phase 3 Interpath-001 trial. The study evaluated 1,137 patients with stage 2B to stage 4 melanoma who had previously undergone complete surgical removal of their tumors. Patients receiving the vaccine alongside Merck's immunotherapy drug Keytruda (pembrolizumab) showed a statistically significant improvement in recurrence-free survival and reduced metastasis compared to Keytruda alone. Two-thirds of participants received Keytruda and up to nine doses of intismeran autogene, while one-third received Keytruda alone. The companies plan to present detailed findings at an upcoming medical conference before seeking regulatory approval.

Moderna chief executive Stéphane Bancel noted the shift toward individualized mRNA treatments.

These Phase 3 findings represent a pivotal moment for the field of cancer research. For many years, the idea of creating an mRNA treatment designed specifically for an individual patient's cancer was aspirational. We are now helping turn that vision into a reality.

Personalized mRNA mechanism and safety

Intismeran autogene, previously known as V940 or mRNA-4157, functions as a personalized therapeutic vaccine. Following tumor surgery, scientists sequence the patient's cancer genome to identify mutational signatures. The mRNA vaccine trains the immune system to recognize up to 34 neoantigens found exclusively on mutated cancer cells, with production taking six weeks. Adding the vaccine caused no new severe side effects beyond known Keytruda toxicities. In a 2022 Phase 2 trial, the combination reduced melanoma recurrence or death by 44% compared to Keytruda alone.

Georgina Long, lead investigator of Interpath-001, described the significance for postsurgical melanoma care.

Today's results represent a milestone for the adjuvant treatment of melanoma. This is the first Phase 3 study showing that intismeran, a treatment designed from the unique mutational genetic footprint of each patient's tumor, administered in combination with pembrolizumab, can reduce the risk of recurrence or death in melanoma patients.

Financial reaction and clinical pipeline

Following the announcement, Moderna shares gained 177% to close at $174.38 on Wednesday, while Merck rose 13% and BioNTech gained nearly 22%. Keytruda generated over $30 billion in revenue for Merck last year, with patents expiring near the end of the decade. Barclays estimates intismeran could generate $3 billion in annual sales by 2035, with a potential 2027 market launch. Moderna and Merck are conducting additional trials in lung, kidney, bladder, and pancreatic cancers. BioNTech and Roche are evaluating autogene cevumeran in colon and pancreatic trials with readouts expected in 2027 and 2031.

Mass General Brigham Cancer Institute melanoma director Ryan Sullivan noted the broader impact on cancer research.

It is a big deal for the field in general. With this positive study, there is hope (and likely investment to follow) that these approaches may change the way we treat cancer more broadly.