Merck and Moderna have reported a landmark Phase 3 success for an individualized mRNA-based cancer treatment, saying their therapy significantly reduced the risk of melanoma recurrence and distant metastasis when combined with KEYTRUDA.

 

The companies said the Phase 3 INTerpath-001 trial met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS) in patients with completely resected stage IIB-IV melanoma.

 

The results mark the first positive Phase 3 readout for an individualized neoantigen therapy and an mRNA-based cancer therapy, according to the companies. They also represent the first Phase 3 study to show a clinically meaningful improvement over KEYTRUDA alone in the adjuvant treatment of resected melanoma.

 

At a pre-specified interim analysis, intismeran autogene (intismeran; V940 or mRNA-4157), an investigational individualized neoantigen therapy being developed by Merck and Moderna, demonstrated statistically significant and clinically meaningful improvements in both RFS and DMFS when added to KEYTRUDA, compared with KEYTRUDA alone.

 

The trial enrolled patients with completely resected stage IIB, IIC, III or IV cutaneous melanoma who had not previously received systemic therapy.

 

The study will continue to assess additional secondary endpoints, including overall survival, in line with the trial protocol.

 

The companies said the safety profiles of intismeran and KEYTRUDA were consistent with earlier studies of the combination, with no new safety signals identified.

 

“Today’s results represent a landmark moment for adjuvant melanoma treatment. This is the first Phase 3 study to show that intismeran, a treatment designed based on the unique mutational ‘fingerprint' of a patient's own tumor, given in combination with pembrolizumab can reduce the risk of recurrence or death in patients with completely resected stage IIB-IV melanoma compared to KEYTRUDA alone,” said Professor Georgina Long, the study’s principal investigator.

 

“Intismeran in combination with pembrolizumab has the potential to establish a new treatment paradigm in the adjuvant melanoma setting, helping patients remain cancer-free for longer.”

 

The companies said the findings will be presented at an upcoming international medical meeting and submitted to regulatory authorities.

 

“By intervening earlier in the course of disease, when many cancers are considered most treatable, the goal of adjuvant therapy given after surgery is to increase the possibility of cure for more patients,” said Dean Y. Li, president, Merck Research Laboratories.

 

“These first Phase 3 findings for intismeran in combination with KEYTRUDA as adjuvant therapy reinforce the promise of a more personalized approach to cancer treatment. We believe individualized neoantigen therapies have the potential to redefine how patients with completely resected stage IIB-IV melanoma are treated. Together with Moderna, we look forward to presenting data from INTerpath-001 at an international medical meeting and sharing with regulatory authorities.”

 

Moderna CEO Stéphane Bancel described the findings as a major milestone for personalized cancer treatment, highlighting the long-standing goal of developing therapies tailored to an individual patient’s tumor.

 

“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,” said Stéphane Bancel, CEO of Moderna. 

 

“Together with Merck, we have started to demonstrate the transformative potential of this technology to address critical unmet needs in the adjuvant melanoma setting. We are deeply grateful to the patients, investigators and study teams whose contributions make this progress possible.”