Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, and Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced the first presentation of detailed results from the Phase 2b KEYNOTE-942/mRNA-4157-P201 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 population, adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in recurrence-free survival (RFS), and reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.309-1.017]; one-sided p value=0.0266) compared with KEYTRUDA alone.

These findings will be presented during the American Association for Cancer Research (AACR) Annual Meeting 2023 plenary session and press conference (Abstract #CT001). Data from a subgroup analysis of KEYNOTE-942/mRNA-4157-P201 (Abstract #CT224) evaluating mRNA-4157 (V940) in combination with KEYTRUDA among patients based on tumor mutational burden (TMB) status will also be presented.

“Today’s results provide further encouragement for the potential of mRNA as an individualized neoantigen therapy to positively impact patients with high-risk resected melanoma,” said Dr. Kyle Holen, M.D. Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. “The profound observed reduction in the risk of recurrence-free survival suggests this combination may be a novel means of potentially extending the lives of patients with high-risk melanoma. We look forward to starting the Phase 3 melanoma trial soon and expanding testing to lung cancer and beyond.”

“Data from KEYNOTE-942 provide evidence for the potential of mRNA-4157 (V940) in combination with KEYTRUDA to improve recurrence-free survival when given to patients with resected high-risk melanoma,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “These data support the potential of mRNA-4157 (V940) in combination with KEYTRUDA to help fight melanoma earlier and warrant investigation of the combination in a larger Phase 3 trial. We also look forward to studying mRNA-4157 (V940) and KEYTRUDA in a variety of other early-stage cancers.”

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 PRIME scheme, respectively, for mRNA-4157 (V940) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk melanoma following complete resection. Additional data from KEYNOTE-942/mRNA-4157-P201 will be shared at an upcoming medical meeting and published in a peer-reviewed publication. The companies previously announced positive data from this study in December 2022.

Additional efficacy and safety data from KEYNOTE-942/mRNA-4157-P201 (Abstract #CT001)

In KEYNOTE-942/mRNA-4157-P201, 107 patients received mRNA-4157 (V940) in combination with KEYTRUDA and 50 patients were treated with KEYTRUDA alone. Recurrence or death was reported in 22.4% of patients (n=24/107) in the combination arm compared with 40% of patients (n=20/50) who received KEYTRUDA alone with a median follow-up of 23 and 24 months, respectively. The 12-month RFS rate was 83.4% (95% CI, 74.7-89.3) and 77.1% (95% CI, 62.5-86.6) in the combination and control arms, respectively. The 18-month RFS rate was 78.6% (95% CI, 69.0-85.6) and 62.2% (95% CI, 46.9-74.3) in the combination and control arms, respectively.

Adverse events reported with mRNA-4157 (V940) in KEYNOTE-942 were consistent with those previously observed in a Phase 1 clinical trial. The safety profile of KEYTRUDA was consistent with findings from previous studies. The number of patients reporting treatment related Grade ≥ 3 adverse events were similar between the arms (25% vs 18%, respectively). The most common adverse events of any grade attributed to either mRNA-4157 (V940) or the combination of mRNA-4157 (V940) and KEYTRUDA were fatigue (60.6%), injection site pain (55.8%) and chills (50.0%).

TMB subgroup analysis from KEYNOTE-942/mRNA-4157-P201 (#CT224)

Data from an exploratory subgroup analysis of KEYNOTE-942/mRNA-4157-P201 showed that improvement in RFS was observed with mRNA-4157 (V940) in combination with KEYTRUDA compared to KEYTRUDA alone regardless of TMB status. TMB was assessed using tumor biopsies analyzed by whole exome sequencing (WES) and whole transcriptome sequencing. According to the established WES genomic score for KEYTRUDA, TMB high was defined as ≥10 mut/Mb (175 mut/exome) assessed using the FoundationOne CDx assay.

The RFS benefit of mRNA-4157 (V940) in combination with KEYTRUDA compared to KEYTRUDA alone observed in the intention-to-treat population was maintained across both TMB high (HR=0.65; 95% CI: 0.284-1.494) and TMB non-high (HR=0.59; 95% CI: 0.243-1.425) subpopulations. The association between TMB and mRNA-4157 (V940) treatment effect will be further explored in upcoming planned studies.