Novel Combination Demonstrated Statistically Significant and Clinically Meaningful Improvement in Distant Metastasis-free Survival

Moderna, Inc. and Merck today announced distant metastasis-free survival (DMFS) results from the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study, a clinical trial evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck's anti-PD-1 therapy, in patients with resected high-risk melanoma (stage III/IV).

In the overall intention-to-treat (ITT) population, adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in DMFS, a key secondary endpoint of the study, compared with KEYTRUDA alone and reduced the risk of developing distant metastasis or death by 65% (HR=0.347 [95% CI, 0.145-0.828]); one-sided p value=0.0063).

The secondary endpoint of DMFS, defined as the time from the first dose of KEYTRUDA until the date of first distant recurrence or death from any cause, was pre-specified for statistical testing following the positive primary endpoint of recurrence-free survival.

"We are excited to share these results with the oncology community and thrilled to see such an exceptional result in distant melanoma recurrence or death. Patients who experience metastases at distant sites typically have worse survival outcomes and a poor prognosis, thus, these results showing a reduction in the risk of distant recurrence underscore the potential of neoantigen therapy," said Kyle Holen, M.D. Moderna's Senior Vice President and Head of Development, Therapeutics, and Oncology, in a press release on June 5, 2023.

Companies plan to initiate a Phase 3 study in the adjuvant setting in patients with high-risk melanoma in 2023 and rapidly expand to additional tumor types, including non-small cell lung cancer.

Based on data from KEYNOTE-942/mRNA-4157-P201, the U.S. Food and Drug Administration and European Medicines Agency granted Breakthrough Therapy Designation and the Priority Medicines scheme, respectively, for mRNA-4157 (V940) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk melanoma following complete resection.