Data from their phase 2b trial, which looked at Moderna’s investigational personalized cancer vaccine, mRNA-4157/V940, in combination with MSD's anti-PD-1 therapy, Keytruda, showed the study met the primary endpoint of recurrence-free survival as an add-on therapy in high-risk skin cancer patients.
Adjuvant treatment with mRNA-4157/V940 in combination with Keytruda reduced the risk of recurrence or death by 44% compared with MSD’s immunotherapy alone, according to the readout.
The ongoing study involved 157 patients with stage III/IV melanoma whose tumors were surgically removed before being treated with the drug/vaccine combo or Keytruda alone with the aim of delaying disease recurrence.
Adverse events observed with mRNA-4157/V940 in KEYNOTE-942 mirrored those previously reported in a Phase 1 clinical trial, while 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 the blockbuster therapy alone, said the companies.
The findings are exciting for the field, said Jeffrey Weber, principal investigator, deputy director of the Perlmutter Cancer Center at NYU Langone, and a paid consultant for MSD and Moderna.
“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."
Moderna said the findings not only mark a positive step forward in potentially revolutionizing the way cancer is treated, but also illustrate the broader power of mRNA technology beyond COVID-19 into other disease areas.
“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," commented Stéphane Bancel, Moderna's CEO. "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."
Training immune systems
Personalized cancer vaccines are individualized medicines designed to train a patient’s immune system to fight their specific cancer more effectively.
mRNA-4157/V940 works by stimulating an immune response through generating specific T cell responses based on the unique mutational signature of a patient's tumor.
Keytruda is an immunotherapy designed to increase the ability of the body's immune system to help detect and fight tumor cells and earlier clinical studies showed that combining mRNA-4157/V940 with Keytruda could potentially provide an additive benefit and enhance T cell-mediated destruction of tumor cells.
The idea now is to advance the program into the next phase of development. Both Moderna and MSD plan to discuss results with regulatory authorities, initiate a phase III study in melanoma in 2023, and expand to additional tumor types.
In October of this year, they announced that MSD had exercised its option to jointly develop and commercialize mRNA-4157/V940. The two entities will share costs and any profits equally under this worldwide collaboration.
Other players in the space
Nykode Therapeutics is also collaborating with MSD in this space. This week the Norwegian company announced that it had entered into a clinical collaboration and supply agreement with the pharma giant to evaluate its wholly-owned lead candidate, VB10.16, in combination with Keytruda in a Phase 1/2a trial in patients with HPV16-positive head and neck cancer.
Among its other investigations in this area, BioNTech has a cancer vaccine trial running with the Memorial Sloan Kettering Cancer Center in New York, which is evaluating the German firm's experimental drug in combination with Roche's Tecentriq in patients with pancreatic cancer.