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Moderna, Merck unveil three-year mid-stage data for vaccine-Keytruda combo in melanoma, with PhIII underway

Moderna and Merck reported Thursday that their personalized melanoma cancer vaccine plus Keytruda approach delivered “continued improvement” in reducing…

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Moderna and Merck reported Thursday that their personalized melanoma cancer vaccine plus Keytruda approach delivered “continued improvement” in reducing risk of disease recurrence or death, based on three-year data from a mid-stage trial.

But debate surrounding the use of one-sided nominal p-values may surface again, much like when the companies heralded success from a primary analysis readout for the same study. The Phase IIb trial recruited 157 high-risk patients who had complete surgical resection of their stage 3 or 4 melanoma.

In the latest primary endpoint data with a median follow-up of three years, mRNA-4157 plus Keytruda reduced the risk of recurrence or death by 49% compared with Keytruda monotherapy, with a one-sided nominal p-value of 0.0095. In the key secondary endpoint of distant metastasis-free survival, the combo reduced the risk of distant metastasis or death by 62% compared with Keytruda (one-sided nominal p=0.0077).

Last year, the companies revealed the combination regimen met the trial’s recurrence-free survival primary endpoint, reducing the risk of recurrence or death by 44% compared with Keytruda (one-sided p=0.0266).

When the first wave of data was released, there were mixed opinions on Moderna and Merck’s use of a one-sided p-value, which looks at just one side of an outcome’s probability, namely the chance that the vaccine had a positive effect. The companies defended their choice, noting one-sided analyses are not an uncommon design element in early-stage trials. But some viewed the companies as trying to present their data in a more favorable light.

As for the trial’s three-year safety data, the vaccine-Keytruda arm saw a 25% rate of grade 3 or higher treatment-related adverse events versus 20% for the Keytruda control. The most common side effects associated with Moderna’s vaccine were fatigue (60.6%), injection site pain (56.7%) and chills (49%).

The mRNA-4157 vaccine is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient’s tumor. Merck and Moderna have officially dubbed this approach individualized neoantigen therapy.

In July, Merck and Moderna announced the start of a Phase III trial of mRNA-4157 plus Keytruda in melanoma. The study, named INTerpath-001, aims to enroll 1,089 subjects and is measuring the primary endpoint of recurrence-free survival at 74 months, according to ClinicalTrials.gov.

Stéphane Bancel

More recently, the partners revealed they had enrolled the first patient into a Phase III trial of mRNA-4157 plus Keytruda in non-small cell lung cancer on Tuesday. The INTerpath-002 study aims to enroll 868 subjects and is measuring the primary endpoint of disease-free survival at 78 months, according to ClinicalTrials.gov.

Moderna’s success in these registrational studies could play an important part in the company’s post-Covid future, expanding from its Spikevax vaccine franchise. CEO Stéphane Bancel previously told Endpoints News that mRNA-4157’s price tag would be comparable to that of CAR-T therapies, which exceed the $300,000 mark.

Melanoma is the most serious form of skin cancer and almost 325,000 new cases were diagnosed worldwide in 2020, according to Moderna.

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