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• Posted April 17, 2023

Therapeutic Cancer Vaccine Boosts Survival for People Battling Advanced Melanoma

An experimental vaccine whipped up to specifically target a melanoma patient's tumor cells significantly reduces the likelihood of the cancer recurring, early clinical trial data show.

Each dose of the vaccine, called mRNA-4157/V940, is crafted based on the unique genetics of an individual patient's melanoma cells, said senior researcher Dr. Jeffrey Weber, deputy director of the Perlmutter Cancer Center at NYU Langone Health in New York City.

When administered alongside an immune-boosting drug, the vaccine reduced the likelihood of melanoma either recurring or causing death by 44% compared to results from the immunotherapy alone, results showed.

The vaccine teaches a person's immune system how to find and target melanoma by looking for neoantigens, or mutated receptors found on cancer cells, Weber said.

"They're only mutated in the tumor, not in the normal tissue,"he said of these receptors. "So by definition, if they could be recognized by the immune system, the immune system would only recognize them on the cancer, it would not recognize normal cells, which is good. That would technically avoid toxicity."

Early attempts at cancer vaccines have tried the same thing with common antigens shared by many tumor cells, but they haven't been specific enough to work well, said Dr. Timothy Yap, medical director of the Institute for Applied Cancer Science at the University of Texas MD Anderson Cancer Center in Houston. He was not involved in this study.

"The investigators really felt that a personalized vaccine that targets an individual's very unique set of cancer neoantigens may overcome this limitation of these previous vaccine approaches,"Yap said.

This clinical trial focused on men and women who had had surgery to remove melanoma from lymph nodes or other organs. Their risk of the cancer coming back was high, "50% or more,"Weber said.

Researchers randomly selected 107 patients to receive the vaccine along with pembrolizumab (Keytruda), an immune therapy drug that is the first-line treatment following surgery for melanoma.

Another 50 patients received pembrolizumab alone. The drug works by blocking a trick that cancer cells use to hide from the immune system.

Vaccine doses took between six and eight weeks to develop, and were crafted based on genetic analysis of the cancer removed from each individual patient.

Using messenger RNA, the vaccine teaches the immune system to recognize as many as 34 different and unique neoantigens found on the cells of their melanoma.

Once unmasked by the pembrolizumab, the cancer cells are then subject to targeted attack by an immune system educated via the personalized vaccine.

Of the 107 patients who received the vaccine/drug combo, cancer returned in 24 (22%), according to results presented Sunday at a meeting of the American Association for Cancer Research, in Orlando, Fla.

By comparison, cancer returned in 40% of people who received immunotherapy alone, or 20 out of 50 patients.

"It's the first randomized trial to demonstrate this relapse-free survival improvement using a personalized neoantigen approach in resected high-risk melanoma,"Yap said. "It really does address a very critically unmet need in these high-risk patients."

Side effects from the vaccine were "the sort of stuff that you and I get when we get a COVID vaccine,"Weber said.

About 11% of patients had significant vaccine-related side effects, but "usually it's people with a temperature over a certain point or who have profound fatigue and were bedbound for a day or so,"Weber said. "It's similar to or perhaps an exaggeration of what you'd see with a COVID or a flu shot."

Based on these findings, the vaccine will progress to a large randomized phase 3 clinical trial with 1,000 patients, Weber said.

If the larger trial starts this summer and the vaccine proves effective and safe, it could be up for approval from the U.S. Food and Drug Administration within three years, Weber estimated.

The vaccine also might prove useful in treating a wide variety of other cancers, Yap and Weber said -- including head and neck cancers, and cancers of the lungs, liver, kidneys and esophagus.

"I think it really provides a platform really to move on to other tumor types, such as non-small cell lung cancer,"Yap said of the new study. "It provides that proof of concept here that we can explore the use of these neoantigen vaccines with, say, pembrolizumab-approved indications at an early stage and also even metastatic setting."

This clinical trial was funded by Moderna, the company that developed the vaccine, and Merck, the manufacturer of pembrolizumab.

Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal.

More information

Dana-Farber Cancer Institute has more about immunotherapy treatments for cancer.

SOURCES: Jeffrey Weber, MD, PhD, deputy director, Perlmutter Cancer Center, NYU Langone Health, New York City; Timothy Yap, MBBS, PhD, medical director, Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston; American Association for Cancer Research Annual Meeting, presentation, April 16, 2023, Orlando, Fla.