Adjuvant treatment with mRNA-4157 (V940) continues to show progress vs. pembrolizumab alone.

Merck and Moderna announced media planned follow-up data for their phase 2b study of mRNA-4157 (V940), which when combined with pembrolizumab (KEYTRUDA), showed continued improvement in recurrence-free survival and distant metastasis-free survival in patients with high-risk stage III/IV melanoma following complete resection.

The three-year results built on primary analysis data presented earlier in 2023, which showed mRNA-4157(V940), an investigational individualized neoantigen therapy, in combination with pembrolizumab was associated with a 44% reduction in the risk of recurrence or death, and a 65% reduction in the risk of distant metastasis or death at approximately two years. The three-year data indicated a 49% reduction (HR=0.510 [95% CI, 0.288-0.906; one-sided nominal P=0.0095) in the risk of recurrence or death, and a 62% reduction (HR=0.384 [95% CI, 0.172-0.858; one-sided nominal P=0.0077) in the risk of distant metastasis. 

“These data add another positive analysis to the multiple endpoints and subgroups previously assessed in this study," said Kyle Holen, MD, Moderna’s Senior Vice President and Head of Development, in a news release. "Therapeutics and Oncology. Importantly for this technology, the KEYNOTE-942/mRNA-4157-P201 study was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and the first combination therapy to show a significant benefit over [pembrolizumab] alone in adjuvant melanoma. We look forward to sharing these data with people impacted by this disease and the broader scientific community.”

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency both granted Breakthrough Study Designation and the Priority Medicines (PRIMES) scheme, respectively, for the combo therapy. The companies announced a pivotal phase 3 trial (INTerpath-001) evaluating the combo therapy in patients with resected high-risk (Stage IIB-IV) melanoma. They have also initiated a phase 3 clinical trial in non-small-cell lung cancer that is currently enrolling globally.