mRNA Cancer Vaccine Shows Promise in Early Trial

An investigational mRNA cancer vaccine met its primary endpoint in a phase IIb study, Moderna and Merck announced Tuesday.

In the KEYNOTE-942 trial, mRNA-4157/V940, in combination with pembrolizumab (Keytruda), reduced the risk of recurrence or death by 44% over 9 months in patients with late-stage melanoma compared with the PD-1 inhibitor alone (HR 0.56, 95% CI 0.31-1.08, P=0.03), the companies said.

In a press release, Moderna CEO Stéphane Bancel called the results "highly encouraging for the field of cancer treatment."

"mRNA has been transformative for COVID-19, and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma," Bancel said.

The trial enrolled 157 patients with stage III/IV melanoma who'd had complete surgical resection of their disease. They were randomized to either the investigational mRNA therapy plus pembrolizumab or pembrolizumab alone. Those in the mRNA arm received nine doses of the therapy, and pembrolizumab was dosed at 200 mg every 3 weeks up to 18 cycles.

Patients were followed until disease recurrence or unacceptable toxicity.

The novel mRNA cancer therapy works by first taking a sample of the patient's tumor, then tailoring the mRNA therapeutic to the tumor's "unique mutational signature," according to the press release. The mRNA can encode for up to 34 neoantigens.

Once the therapy is administered, the sequences for those neoantigens are translated, and then presented to the immune system, where they're recognized by T cells that get rid of them and future antigens.

Essentially, the T cells are trained to detect any new cancer growth, according to Endpoints News, which reported that the process takes about 45 days from sample to treatment.

Adverse events were consistent with those seen in a phase I trial for the mRNA therapy, according to the companies. Serious treatment-related adverse events occurred in 14.4% of those in the combination therapy arm versus 10% in the pembrolizumab-alone arm.

Moderna and Merck are in talks with the FDA and plan to start a phase III study in melanoma in 2023. Eventually, they also plan to expand into other cancer types, according to reports.

Bancel said the company plans to share the results at an upcoming oncology conference.

mRNA rival drugmaker BioNTech is also working on an mRNA cancer vaccine for advanced melanoma, according to reports. That therapy is in phase II trials and is paired with the PD-1 inhibitor cemiplimab-rwlc (Libtayo) made by Regeneron and Sanofi.

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