Cancer Vaccine Could Go ‘Above and Beyond Standard of Care’ For Patients

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Moderna and Merck have initiated V940-001, a phase 3 study evaluating vaccine mRNA-4157 and anti-PD-1 therapy Keytruda as postsurgical treatment for stage 2B to 4 melanoma.

Image of a cancer vaccine vial with a syringe and a blue rubber glove in the background.

The future of potentially approved mRNA cancer vaccines is on the horizon, experts said.

The oncology community is on the cusp of a sea change regarding cancer vaccines, as one expert tells CURE®.

“Current vaccines have a dismal record, and minimal evidence of efficacy,” said Dr. Jeffrey S. Weber, deputy director of the NYU Langone Perlmutter Cancer Center and Laura and Isaac Perlmutter Professor of Oncology at NYU Grossman School of Medicine, via email.

Weber was among the researchers on a recent KEYNOTE-942 study, the results of which were published in The Lancet, investigating mRNA vaccine mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT), and Keytruda, an anti-PD-1 therapy, versus standalone Keytruda for the treatment of patients with advanced-stage melanoma.

“This mRNA vaccine would be the first approved cancer vaccine with clear-cut evidence of efficacy in a well-done phase III trial [which was recently initiated],” Weber said of mRNA-4157.

Pharmaceutical companies Moderna and Merck have initiated V940-001, a phase 3 study evaluating mRNA-4157 and Keytruda as postsurgical treatment for stage 2B to 4 melanoma, announcing in June of 2023 that global patient recruitment had begun following primary analysis of the findings of KEYNOTE-942.

“As we continue our efforts to advance novel treatment options for patients with high-risk stage 2B to 4 melanoma, the initiation of the V940-001 phase 3 trial represents an important step forward in these efforts and our study of individualized neoantigen therapy,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in a news release. “We look forward to continuing to collaborate with Moderna to evaluate this promising new approach with V940 [mRNA-4157], while also building on a standard of care laid by Keytruda.”

In the KEYNOTE-942 trial, 157 patients with stages 3B to 4 melanoma that was completely resected (surgically removed) high-risk cutaneous melanoma were assigned to be treated with mRNA-4157 and Keytruda (107 patients) or Keytruda alone (50 patients). With a median follow-up of 23 and 24 months, the recurrence or death rates were 22% and 40% and the 18-month recurrence-free survival rates were 79% and 62%, respectively.

Most treatment-related side effects were grades 1 or 2, with grade 3 (mild to severe side effects) or higher treatment-related side effects occurring in 25% of patients who were treated with the combination regimen and 18% of patients treated with Keytruda monotherapy and no grade 4 or 5 side effects related to mRNA-4157. In both patient cohorts, immune-mediated side effect event frequency was 36%.

The Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to the combination for the post-surgical treatment of patients with high-risk melanoma in 2023 based on the results of KEYNOTE-942.

Weber urged patients with melanoma in conversations with their care providers to “do their best to get on a neoantigen vaccine trial.”

“There is a good chance that adjuvant (postsurgical) neoantigen vaccines will enter the armamentarium in the next few years and provide incremental benefit for patients above and beyond the standard of care [Keytruda, a] PD-1 blockade,” Weber said.

“The initiation of the V940-001 phase 3 trial is an exciting and important milestone for us as we work with our colleagues at Merck and the melanoma patient community to investigate how individualized neoantigen therapy may potentially transform the treatment of the most serious form of skin cancer,” said Dr. Kyle Holen Moderna's senior vice president and head of development, therapeutics and oncology, in the news release.

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