Initial Efficacy Demonstration for an Investigational mRNA Cancer Treatment

Moderna, Inc., and Merck today announced that the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial of mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with KEYTRUDA®, Merck's anti-PD-1 therapy, demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of recurrence-free survival (RFS) versus KEYTRUDA alone for the adjuvant treatment of patients with stage III/IV melanoma following complete resection.

Adjuvant treatment with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.31-1.08]; one-sided p-value=0.0266) compared with KEYTRUDA alone.

The companies plan to discuss the results with regulatory authorities and initiate a Phase 3 study in melanoma patients in 2023.

"Today's results are highly encouraging for the field of cancer treatment. mRNA has been transformative for COVID-19, and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma," stated Stéphane Bancel, Moderna's CEO, in a press release on December 13, 2022.

"We will begin additional studies in melanoma and other forms of cancer with the goal of bringing truly individualized cancer treatments to patients."

"We look forward to publishing the full data set and sharing the results at an upcoming oncology medical conference and with health authorities."

Adverse events observed with mRNA-4157/V940 in KEYNOTE-942 were consistent with those previously reported in a Phase 1 clinical trial.

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies.

Serious treatment-related adverse events occurred in 14.4% of patients who received the combination arm of mRNA-4157/V940 and KEYTRUDA versus 10% with KEYTRUDA alone.

Personalized cancer vaccines are designed to prime the immune system so patients can generate a tailored antitumor response specific to their tumor mutation signature.

mRNA-4157/V940 is a novel investigational messenger ribonucleic acid (mRNA)-based personalized cancer vaccine consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor.

Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.