Merck and Moderna announced positive topline results from the Phase 3 INTerpath-001 trial, evaluating intismeran autogene (V940/mRNA-4157) plus Keytruda (pembrolizumab) as adjuvant treatment for patients with completely resected stage IIB-IV cutaneous melanoma.
The trial met its primary endpoint of recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS). At a prespecified interim analysis, the combination demonstrated statistically significant and clinically meaningful improvements in both endpoints compared with Keytruda alone. Detailed Phase 3 efficacy results have not yet been disclosed.
According to Merck and Moderna, the findings represent the first positive Phase 3 readout for an individualized neoantigen therapy and for an mRNA-based cancer therapy. The study will continue to evaluate other key secondary endpoints, including overall survival (OS).
The safety profiles of intismeran autogene and Keytruda were consistent with those reported in previous studies of the combination, with no new safety signals observed.
Georgina Long, principal investigator of INTerpath-001 and Medical Director of Melanoma Institute Australia, said:
“Today’s results represent a landmark moment for adjuvant melanoma treatment.”
She added that the combination has the potential to establish a new treatment approach in the adjuvant melanoma setting and help patients remain cancer-free for longer.
Dean Y. Li, President of Merck Research Laboratories, said:
“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.”
Merck and Moderna said the data will be presented at an upcoming international medical meeting and shared with regulatory authorities.
About INTerpath-001
INTerpath-001 (NCT05933577) is a randomized, double-blind, placebo- and active-comparator-controlled global Phase 3 trial evaluating intismeran autogene plus Keytruda versus Keytruda alone in patients with high-risk, completely resected stage IIB-IV cutaneous melanoma.
The study enrolled 1,137 patients, who were randomized 2:1 following complete surgical resection. Patients in the combination arm received intismeran at 1 mg every three weeks for up to nine doses together with Keytruda at 400 mg every six weeks for up to nine cycles. Patients in the comparator arm received Keytruda alone for approximately one year. Treatment continued until disease recurrence, unacceptable toxicity, or a total duration of approximately 56 weeks, whichever occurred first.
The trial’s primary endpoint is RFS, defined as the time from randomization to disease recurrence or death from any cause. Key secondary endpoints include DMFS, OS, safety, tolerability, and quality of life.
About Intismeran Autogene
Intismeran autogene, also known as V940 or mRNA-4157, is an investigational mRNA-based individualized neoantigen therapy jointly developed by Merck and Moderna.
The therapy is designed using a sample of an individual patient’s tumor to identify its unique mutational signature. Each treatment contains synthetic mRNA encoding up to 34 neoantigens, selected based on the biology of that patient’s tumor, to generate tumor-specific immune responses.
Merck and Moderna are evaluating intismeran through the broader INTerpath clinical development program, which includes Phase 2 and Phase 3 studies across several tumor types and disease stages.
About Keytruda
Keytruda (pembrolizumab) is Merck’s anti-PD-1 therapy. It is a humanized monoclonal antibody that blocks the interaction between the PD-1 receptor and its ligands, PD-L1 and PD-L2, helping activate T-cell-mediated immune responses.
In the U.S., Keytruda is approved for several melanoma indications, including the treatment of unresectable or metastatic melanoma and as adjuvant therapy for adult and pediatric patients aged 12 years and older with completely resected stage IIB, IIC, or III melanoma.
Merck is evaluating Keytruda across a broad immuno-oncology clinical development program, including combinations with investigational therapies such as intismeran autogene.
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