Vaccine May Help Reduce Relapse in High-Risk Melanoma Patients

ORLANDO, Fla. — A personalized mRNA-based cancer vaccine, when combined with Merck cancer therapy Keytruda, resulted in a statistically significant improvement in recurrence-free survival in people who had surgery to remove a cancerous tumor, compared with using Keytruda alone.

That was the conclusion of researchers from Moderna, who presented the results of their phase IIb KEYNOTE-942 clinical trial at the annual meeting of the American Association of Cancer Research this past weekend in Orlando.

The results, which were originally announced by Merck in December, showed the combined treatment reduced the risk of death or recurrence of melanoma, by 44% compared with Keytruda alone.

“Vaccine strategies over the last 25 years attempted to induce immune responses against tumor-associated antigens that are not absolutely specific to the tumor,” said presenting author Dr. Jeffrey Weber, Ph.D., deputy director of the NYU Langone Perlmutter Cancer Center and Laura and Isaac Perlmutter Professor of Oncology at NYU Grossman School of Medicine. 

“More recent cancer vaccine approaches have focused on targeting neoantigens originated from individual tumor mutations, which are unique to cancer cells,” he said.

Weber conducted the research with funding from the two pharmaceutical companies.

According to a press release on the American Association of Cancer Research’s website, mRNA-4157/V940 is a novel mRNA-based personalized cancer vaccine that encodes up to 34 patient-specific tumor neoantigens. 

In addition to encoding the target antigens, mRNA vaccines also provide adjuvant properties that amplify the immune response.

The randomized KEYNOTE-942 trial assessed the efficacy of mRNA-4157/V940 in prolonging RFS in patients with resected, stages IIIB/IIIC/IIID and IV melanoma when given in combination with pembrolizumab, the standard-of-care adjuvant therapy in this patient population. 

Patients were randomly assigned (2:1) to receive mRNA-4157/V940 in combination with pembrolizumab (107 patients) or pembrolizumab alone (50 patients). The vaccine was administered every three weeks for a total of nine doses, and pembrolizumab was given every three weeks for up to 18 cycles.

The results of the primary trial analysis showed, after 18 months, the RFS was 78.6% in the combination arm and 62.2% in the pembrolizumab arm, corresponding to a 44% reduction in the risk of recurrence or death in patients who received both mRNA-4157/V940 and pembrolizumab compared to those who only received pembrolizumab. 

The majority of treatment-related adverse events were mild, and the rates of serious adverse events were comparable between the two arms, Weber said.

According to Weber, one limitation of the KEYNOTE-942 trial is that, although randomized, it is a phase IIb study with modest statistical power.

“Overall, it is a small number of patients, and one has to be cautious with the interpretation of the results,” Weber said. “A larger, phase III randomized study to confirm our findings will begin soon.”

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