Neoantigen Vaccine With Pembrolizumab Has Clear Benefit in Resected Melanoma

Jeffrey S. Weber, MD, PhD


March 01, 2023

This transcript has been edited for clarity.

I'm Dr Jeffrey Weber, a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health in New York City. Today, I'm reporting to you not on a presentation at a meeting or on a published communication, but on a press release, which I think has very important implications for the field of oncology.

It's a press release that came out recently from both Moderna and Merck, who have collaborated on a clinical vaccine trial. [Editor’s note: Dr Weber is the principal investigator of this trial.]

In the trial, patients with high-risk resected stage IIIB/IIIC and IV melanoma were randomly allocated in a 2-to-1 ratio in a randomized phase 2 study to receive a neoantigen RNA lipid-encapsulated vaccine from Moderna with pembrolizumab, the programmed cell death protein 1 (PD-1) antibody, vs pembrolizumab alone. A total of 157 patients were randomized, with 107 and 50 patients receiving vaccine pembrolizumab vs pembrolizumab alone, respectively.

The results of the study — of which there are relatively few details — were released 2 days ago in a press release showing that the trial met its endpoint of improvement in relapse-free survival with a hazard ratio of 0.56, which reflects a 44% reduction in the risk for relapse in the combination arm vs pembrolizumab alone. The P value, which was a one-sided P value because this was a randomized phase 2 study of limited size, was .026.

These are very interesting and impressive data, albeit preliminary data in a randomized phase 2 study. Why is this important? This is a study with results that will, of course, come out in a peer-reviewed publication in the next couple of months. At this point, it's important for three major reasons.

One, it's the first time that anyone has been able to show in a randomized trial that you can improve upon the benefit of adjuvant PD-1 blockade in patients with high-risk resected melanoma. Second, perhaps more importantly, in melanoma, it's the first time that there's clear evidence of benefit in a randomized setting of a neoantigen vaccine approach.

Vaccines in cancer have a long history of lack of benefit, and failure. This would represent the first randomized study in which there is clear-cut benefit for a neoantigen approach to a vaccine strategy in patients with resected melanoma.

Furthermore, it has many implications, not only in melanoma but also in other malignancies because there's no reason why this neoantigen strategy, using an RNA lipid-encapsulated vaccine to generate immune responses against multiple neoantigens encoded within the tumor, couldn’t be applied to other malignancies, especially those that are immunogenic and have some sensitivity to PD-1 blockade, such as non–small cell lung cancer, head and neck cancer, renal cell carcinoma, and esophageal and gastric carcinoma.

This could be a game changer in that it opens the possibility for multiple potential randomized clinical trials in the adjuvant mode in patients with resected high-risk cancer.

Finally, it does take 6-8 weeks to prepare the vaccine, so the adjuvant mode is the perfect scenario in which to test this concept.

This is Dr Jeffrey Weber, reporting on what I think is a very impactful and interesting press release from Moderna and Merck on a randomized phase 2 trial of a neoantigen vaccine with pembrolizumab vs pembrolizumab alone.

Please feel free to call in with comments or issues. Thank you very much.

Jeffrey Weber, MD, PhD, is deputy director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center and co-director of its Melanoma Research Program. His research, which has been continuously funded by the NCI for more than 20 years, focuses on experimental therapeutics and drug development, particularly in immunotherapy.

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