MRNA-4157/V940 a personalised MRNA cancer vaccine + Keytruda met primary efficacy endpoint in phase IIB KEYNOTE 942 trial to treat melanoma

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.

"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," said Stéphane Bancel, Moderna's Chief Executive Officer. "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, as well as with health authorities."

"The results of this randomized Phase IIb trial are exciting for the field. These data provide the first evidence that we can improve on the rates of recurrence-free survival achieved by PD-1 blockade in resected high-risk melanoma. These findings also provide the first randomized evidence that a personalized neoantigen approach may be beneficial in melanoma," said Jeffrey S. Weber, MD, PhD, principal investigator of the study and Deputy Director of the Perlmutter Cancer Center at NYU Langone. Dr. Weber is a paid consultant for Merck and Moderna.

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 Keytrruda alone.

Personalized cancer vaccines are designed to prime the immune system so that a patient can generate a tailored antitumor response specific to their tumor mutation signature. mRNA-4157/V940 is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient's tumor. Keytruda is an immunotherapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Based on early clinical studies, combining mRNA-4157/V940 with Keytruda may potentially provide an additive benefit and enhance T cell-mediated destruction of tumor cells.

About KEYNOTE-942/mRNA-4157-P201 ( NCT03897881 ): KEYNOTE-942 is an ongoing randomized, open-label Phase IIb trial that enrolled 157 patients with stage III/IV melanoma. Following complete surgical resection, patients were randomized to receive mRNA-4157/V940 (nine total doses of mRNA-4157) and Keytruda(200 mg every three weeks up to 18 cycles [for approximately one year]) versus Keytruda alone for approximately one year until disease recurrence or unacceptable toxicity. The primary endpoint is recurrence-free survival, and secondary endpoints include distant metastasis-free survival and safety. Key eligibility criteria for the trial included: patients with resectable cutaneous melanoma metastatic to a lymph node and at high risk of recurrence, patients with complete resection within 13 weeks prior to the first dose of Keytruda, patients were disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases, patients had a formalin fixed paraffin embedded (FFPE) tumor sample available suitable for sequencing, Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 and patients with normal organ and marrow function reported at screening.