With Merck Footing the $200M Bill, Moderna Launches mRNA Cancer Vaccine Clinical Trial

Moderna Therapeutics announced that it has dosed its first patient in a Phase I trial of mRNA-4157, a messenger RNA (mRNA)-based personalized cancer vaccine.

Behind that statement is a very complicated story. Moderna focuses on mRNA technology, which seems like a great idea in theory but has been extremely difficult in practice. mRNA delivers the messages for DNA to code for proteins. So, in theory, therapeutics based on mRNA would involve engineering an mRNA to do specific things, for example, code for a specific protein or enzyme, and let the body do the actual manufacturing of it.

In the case of this clinical trial, the patient’s name is Glenda Cleaver, 67. A piece of cancer tissue 1-millimeter square, was collected from her right lung at the Sarah Cannon Research Institute in Nashville, Tennessee. It was sent along with a blood sample to Kentucky, then to a facility on the West Coast, where it was scanned for the tumor’s genetic code, compared to the genetic code in the blood.

Bloomberg writes, "For Cleaver, Moderna’s software produced a list of 20 protein targets specific to her cancer. Then its scientists assembled DNA building blocks to create the recipe for her treatment. Those DNA templates were sent to Catalent Biologics in Madison, Wisconsin, where they were transcribed into mRNA and packed as a string of instructions into a little glass vial."

Which was then returned to the research institute and Cleaver was injected with the vaccine. In her case, the tumor had been removed, but there’s always a possibility some of the cells had metastasized and the cancer might return. This vaccine, if it works, will prevent that by allowing Cleaver’s immune system to be all primed and ready to attack those cancer cells unique to her.

The study is funded by Merck, because it also involves use of the company’s checkpoint inhibitor, Keytruda.

"Our goal in this important collaboration is to deliver personalized vaccines to patients suffering from malignant disease, with the hope that this stimulus will generate a tumor-specific immune response in the presence of Keytruda, our approved immune-stimulatory cancer therapy," said Roger Perlmutter, president of Merck Research Laboratories, in a statement. "This trial leverages advances in genomics, advanced data analytics, and immunology to permit the generation of personalized cancer vaccines, a potentially transformative approach to cancer treatment. We are hopeful that this collaboration with Moderna, now entering clinical trials, will yield tangible benefits for cancer patients."

Moderna hopes to enroll up to 90 patients in the trial, called KEYNOTE-603.

If the process sounds labor-intensive and likely expensive, it’s because it is. Any personalized immuno-oncology therapy tends to be, although it’s about as close to a miracle cure as cancer has ever seen. And maybe Moderna’s approach will be another miracle. But it’s receiving some comparisons to Dendreon Corp., whose prostate-cancer vaccine Provenge was approved in 2010. The treatment cost $93,000, was time-consuming and labor-intensive, and had minimal benefit. In 2014, the company was forced to file bankruptcy.

And Moderna isn’t the only company working in this space. BioNTech has partnered with Roche’s Genentech for a therapy for skin cancer. Neon Therapeutics is expecting results from its first study in melanoma, non-small cell lung cancer and bladder cancer early next year.

Merck is funding the trial with $200 million. "We don’t like doing it alone when the biology risk is high," Moderna’s chief executive officer, Stephane Bancel, told Bloomberg. "With Merck, if it goes to zero we won’t lose capital. If it works we’ll take 50 percent of the upside."

The company expects initial results from this trial by the end of 2018. Keytruda has a list price of $150,000 annually, and no one really knows yet how much this approach would cost if it works, but the math suggests probably a lot. Ronald Levy, a professor of medicine at Stanford University, told Bloomberg, "The more personalization is involved, the more cost and logistical challenges—so the result has to justify the extra effort and expense to do it."

Success or failure, the results of this trial are likely to have a big impact on the future of cancer vaccines.