John Theurer Cancer Center Investigators Part of New Study Showing Investigational mRNA Vaccine Plus Immunotherapy Reduced Recurrence of Melanoma Compared to Drug Alone

The results of a new clinical study presented at the American Association of Cancer Research meeting today showed that an investigational messenger RNA (mRNA) vaccine, used in combination with an FDA-approved immunotherapy for certain cancers, reduced the possibility of melanoma, the most serious type of skin cancer, from reoccurring or causing death by 44 percent, compared to use of the immunotherapy alone. Dr. Andrew Pecora at the John Theurer Cancer Center campus, (part of Hackensack Meridian Health) in Hackensack New Jersey, worked collaboratively with NCI designated Georgetown Lombardi Comprehensive Cancer Center Consortium (which JTCC is a part of) and with other national investigators in this phase II clinical trial.

The study, “mRNA-4157 (V940), a Personalized Cancer Vaccine, in Combination with Pembrolizumab, Demonstrates Trend for Improved Recurrence-Free Survival Compared to Pembrolizumab Alone in Adjuvant Melanoma Patients Across Tumor Mutational Burden Subgroups,” enrolled men and women who had surgery to remove melanoma from lymph nodes or other organs. The patients studied were at high risk of the cancer returning in areas of their body distant from the original cancer.

Among 107 study participants who received both the investigational vaccine and the immunotherapy drug, the cancer recurred in 24 patients (22.4 percent) within two years of follow-up, compared with 20 patients out of 50 (40 percent) who received only the immunotherapy, pembrolizumab.

The vaccine, similar to many of the vaccines for COVID-19, is based on messenger RNA, which provides instructions for cells to make proteins. Messenger RNA cancer vaccines are designed to teach the body’s immune system to recognize cancer cells as different from normal cells. In this case, the vaccine strives to trigger an immune response to specific abnormal proteins called “neoantigens” that are made by cancer cells.

Because the study participants all had their tumors removed, researchers were able to analyze their cells for neoantigens that were specific to each melanoma and create a personalized vaccine for each patient. As a result, T cells were produced specific to the neoantigen proteins encoded by the mRNA. Those T cells could then attack any melanoma cells attempting to grow.

“The science employed in this study and its results are particularly exciting because they demonstrate how immunotherapy is being taken to the next level by educating the patient’s immune system with their own cancer cells to recognize and attack their specific cancer through the mRNA technology,” said study co-investigator Andrew Pecora, MD, FACP, a skin-cancer specialist at the John Theurer Cancer Center at Hackensack University Medical Center. “Using mRNA technology allows isolation of the RNA that results in the production of proteins that are specific to antigens to be recognized by the immune system.”

“We are proud to have participated in the mRNA-4157-P201/Keynote-942 trial at the Georgetown Lombardi Comprehensive Cancer Center. In this randomized phase 2 study involving resected high-risk melanoma patients, the combination of the personalized cancer vaccine (mRNA-4157) in combination with pembrolizumab showed a significant improvement in recurrence free survival over pembrolizumab alone,” said Geoffrey T. Gibney, MD, co-leader of the Melanoma Disease Group at the Lombardi Comprehensive Cancer Center. “If confirmed in the upcoming phase III study, this novel strategy for treating high-risk melanoma patients will lead to better survival outcomes and may also be applicable to patients with other aggressive cancer types.”

“This is the future of cancer care, that cancer vaccines would be specific enough to target an individual’s specific cancer as a part of individualized care,” says Andre Goy, M.D., M.S., Chairman and Director of John Theurer Cancer Center (JTCC). “We are honored to be a part of this work and look forward to discovering more approaches that offer clinical benefits to patients.”

“Immunotherapy has revolutionized the field of cancer therapy and offers hope to patients with melanoma and other potentially deadly cancers,” said co-investigator Louis M. Weiner, MD, director of the Georgetown Lombardi Comprehensive Cancer Center. “This study illustrates the power of immunotherapy to fundamentally change the nature of the functional interactions between people and their cancers, and establishes a platform for future progress.”

Promising clinical research with this vaccine has resulted in the U.S. Food and Drug Administration granting Breakthrough Therapy Designation to mRNA-4157/V940 in combination with pembrolizumab, a designation that may reduce the length of FDA review of clinical trial results.

The study was funded by Moderna Inc. of Cambridge, Mass. and Merck of Rahway, NJ. mRNA-4157/V940 is being jointly developed and commercialized by Moderna and Merck. Merck manufactures pembrolizumab.

According to the American Cancer Society, about 97,000 new cases of melanoma will be diagnosed in the U.S. in 2023, and almost 8,000 people are expected to die from this disease.