Keytruda, mRNA Combination Cancer Vaccine Meets Primary Endpoint in Phase 2 Trial

Investigators found that mRNA-4157/V940 (Moderna), an investigational personalized mRNA cancer vaccine, in combination with pembrolizumab (Keytruda; Merck), an anti-PD-1 therapy, demonstrated a clinically meaningful and statistically significant improvement in the primary endpoint of recurrence-free survival (RFS) for individuals with stage 3/4 melanoma following complete resection compared with pembrolizumab alone.

The adjuvant treatment with mRNA-4157/V940 in combination with pembrolizumab reduced the risk of recurrence or death by 44% compared with pembrolizumab alone.

“We have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma,” Stéphane Bancel, MBA, CEO of Moderna, said in a statement.

“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,” Bancel said.

Personalized cancer vaccines are designed to help the immune system tailored to each patient for antitumor responses that are specific to their tumor mutation signature.

mRNA-4157/V940 is designed to stimulate immune response by generating specific T cell responses based on the mutational signature of a patient’s tumor. Pembrolizumab is an immunotherapy that increases the ability of the body’s immune system to detect and fight cancer cells.

Results of earlier clinical studies of the combination have shown the potential to provide an additive benefit and enhance T cell-mediated destruction of tumor cells.

The adverse events (AEs) observed with mRNA-4157/V940 in KEYNOTE-942 (NCT03897881) were generally consistent with those previously reported in phase 1 clinical trials.

Additionally, the safety profile of pembrolizumab was consistent with that observed in previously reported studies.

Investigators reported that approximately 14.4% of individuals who received the combination arm experienced serious treatment-related AEs compared with 10% with pembrolizumab alone.

“The results of this randomized Phase 2b trial are exciting for the field. These data provide the first evidence that we can improve on the rates of (RFS) 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,” Jeffrey S. Weber, MD, PhD, principal investigator of the study and deputy director of the Perlmutter Cancer Center at NYU Langone, said in a statement.

Both companies plan to share results with regulatory authorities and initiate a phase 3 study for individuals with melanoma in 2023.

In October 2022, the companies announced that Merck had exercised its option to jointly develop and commercialize mRNA-4157/V940. Both companies will share costs and any profits equally under the collaboration.

KEYNOTE-942 is an ongoing open-label, phase 2b, randomized trial that enrolled 157 individuals with stage 3/4 melanoma. Following complete surgical resection, individuals were randomized to receive mRNA-4157/V940, in a total of 9 doses, and pembrolizumab, ever 3 weeks for up to 18 cycles, or pembrolizumab alone for approximately 1 year until disease recurrence or unacceptable toxicity.

Reference

Moderna and Merck announce mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with Keytruda (pembrolizumab) met primary efficacy endpoint in phase 2b KEYNOTE-942 trial. Merck. News release. December 13, 2022. Accessed December 14, 2022. https://www.merck.com/news/moderna-and-merck-announce-mrna-4157-v940-an-investigational-personalized-mrna-cancer-vaccine-in-combination-with-keytruda-pembrolizumab-met-primary-efficacy-endpoint-in-phase-2b-keynote-94/