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Apr 16, 2023 · Jeffrey Weber, deputy director of the NYU Langone Perlmutter Cancer Center, presented results from the phase IIb KEYNOTE-942 trial at the AACR Annual Meeting 2023. The trial evaluated the efficacy of mRNA-4157/V940, a personalized mRNA-based cancer vaccine, in combination with pembrolizumab for patients with high-risk melanoma.
- Overview
- Personalized cancer vaccine shows benefit
In 2019, Gary Keblish got a diagnosis from his surgeon that left him stunned. The flat, dark-brown mole he’d had on his back for as long as he could remember had turned into a melanoma that was already advanced, putting him at risk of dying.
“I felt numb,” the Brooklyn teacher, 61, said in an interview.
Fortunately, Keblish was able sign on for a small clinical trial testing a preventive vaccine that might possibly keep the disease from coming back.
The trial focused on a personalized vaccine using mRNA technology that used mutations to target mutations unique to a patient’s cancer but not the healthy cells in the body. All participants in the trial would receive the immunotherapy drug Keytruda (pembrolizumab), the standard of care for high-risk melanoma patients like Keblish. Two-thirds of the participants would also receive the vaccine.
Keblish was one of those who received the vaccine — which teaches the body’s immune system to recognize cancer cells as different from normal cells so that, working along with the immunotheraoy drug, it can attack them.
After two years, Keblish's cancer hasn't returned.
On Sunday, the results of the phase 2 trial, which showed that the combination of the vaccine and immunotherapy reduced the risk of recurrence by nearly half, were presented at the annual meeting of the American Association for Cancer Research.
It's the first randomized, controlled trial to show a benefit from this type of cancer vaccine, said senior investigator Dr. Jeffrey Weber, a deputy director of NYU Langone’s Perlmutter Cancer Center and a professor of medicine at the NYU Grossman School of Medicine.
To test the effectiveness of the vaccine, the international team of researchers recruited 157 melanoma patients whose tumors had been surgically removed and who were at high risk of experiencing a recurrence of their cancers. Fifty patients received only the immunotherapy medication and 107 also got the personalized vaccination.
One of the ways cancer evades the immune system is to fool the body into thinking the threat is over, at which point the natural braking system that prevents the immune system from staying constantly on kicks in. Weber compares the way pembrolizumab works to cutting a stuck brake cable on a car so it can go forward.
Once the system’s braking system has been partially disabled, “the immune system works really well,” Weber said, adding that the downside of “cutting brake cable” is that the immune system stays turned up and some people end up with inflammation and something that resembles an autoimmune disease.
One other way cancer can avoid being destroyed is through mutations, so the immune system’s soldiers cease to recognize it as a threat.
NYU Langone oncologist Dr. Jeffrey Weber is a specialist in melanoma management and cancer immunotherapy. Learn more.
Apr 16, 2023 · Dr. Jeffrey Weber, who led the new study and is the deputy director of the Perlmutter Cancer Center at NYU Langone, said he's optimistic about the future of mRNA vaccines against cancer.
Jeffrey S. Weber, MD, PhD, to Serve as Deputy Director of the Laura and Isaac Perlmutter Cancer Center, Co-Director of its Melanoma Program & Head of Experimental Therapeutics.
Apr 16, 2023 · NYU Langone researcher Dr. Jeffrey S. Weber led a clinical trial that found adding a vaccine to an immunotherapy reduced melanoma recurrence. Learn more.
Apr 20, 2023 · Reporting from AACR 2023, Jeffrey S. Weber presents the results from primary analysis of the KEYNOTE-942 trial, testing a combination of pembrolizumab plus a novel mRNA-based vaccine based on personalised neoantigens from patients with high-risk resected melanoma, compared to pembrolizumab alone.
