A cancer vaccine based on the messenger RNA (mRNA) technology, provided alongside the checkpoint inhibitor pembrolizumab (Keytruda), has shown encouraging results in an open label phase 2b clinical trial. The trial found that the combination regimen reduced the risk of cancer recurrence or death among melanoma patients by 44% compared with pembrolizumab alone, according to the vaccine’s manufacturer Moderna.
Here are four things to know about the mRNA-4157/V940 cancer vaccine and what the company has in store for upcoming clinical trials.
1. The mRNA vaccine is personalized
Moderna’s mRNA vaccine is personalized for each patient. The vaccine is designed to prime the immune system in a way that allows a patient to generate a tailored antitumor response specific to their tumor mutations.
To identify a patient’s specific mutations, researchers sequence DNA from the patient’s normal tissue as well as DNA from the tumor. Results are compared to identify a set of mutations unique to the patient’s cancer. Researchers then develop a single synthetic mRNA coding for up to 34 neoantigens, designed based on the tumor’s specific mutational signature. The aim is for mRNA-4157/V940 to help the patient’s immune system identify and attack the tumor cells only.
2. Development, distribution happens quickly
The process of personalizing the vaccine happens over several weeks, according to Moderna’s Head of Development for Oncology Kyle Holen.
By itself, “the RNA sequencing takes only 2 hours to develop, which is just mind-boggling that it can happen so quickly,” Holen said. “It’s important to do this quickly because patients with cancer don’t have much time to wait.”
After acquiring samples from patients, sequencing, running the algorithm to identify specific mutations, manufacturing the RNA, and delivering the vaccine to patients take about 6 weeks in total.
3. Adverse events higher in the experimental arm
Serious treatment-related events occurred in 14.4% of patients who received the combination of mRNA-4157/V940 and pembrolizumab vs 10% receiving pembrolizumab monotherapy. The adverse events observed were consistent with those seen in phase 1 of the trial, and Moderna did not report any events in the phase 2b trial.
4. Moderna’s plans to expand beyond melanoma
Moderna is still developing a phase 3 clinical trial for mRNA-4157/V940, which the company hopes to launch sometime in 2023, Holen said during a press conference. Moderna also plans to expand its personalized mRNA vaccine approach beyond melanoma to other tumor types but has not begun that expansion yet.