In an encouraging development for the concept of using vaccines to fight cancer, a personalized messenger RNA (mRNA) cancer vaccine jointly developed by Moderna and Merck Co. has shown positive results in a randomized Phase 2 clinical trial, the companies announced Dec. 13.
The shot, when combined with Merck’s checkpoint inhibitor Keytruda, reduced the risk of cancer recurrence or death by 44% compared to Keytruda alone over a period of 1 year. It was tested in people with stage 3/4 melanoma who had their tumors removed but had a higher chance of the cancer returning due to features of their melanoma, said Michelle Brown, Moderna’s program director for oncology, in a Dec. 14 roundtable with reporters.
Moderna and Merck say they are the first companies to show efficacy in a randomized clinical trial for an investigational mRNA-based cancer treatment. “This profound clinical benefit for patients really substantiates the idea of a personalized cancer vaccine,” Brown said in the roundtable. “And it also really gives us confidence in the potential for mRNA in oncology patients.”
Some vaccines to treat cancer are already approved, but they haven’t shown a substantial survival benefit, and not all have a clear mechanism of action, says Andrew Allen, CEO of Gritstone Bio, which is developing vaccines for cancer as well as infectious diseases.
The Moderna/Merck vaccine is personalized, meaning the mRNA sequences it delivers are tailored to each patient. And it is intended to prevent recurrence of cancer rather than prevent cancer in the first place. But in other ways, the jab is similar to mRNA vaccines for COVID-19.
mRNA COVID-19 vaccines, such as Moderna’s SpikeVax or Pfizer and BioNTech’s Comirnaty, introduce to the body a piece of mRNA that encodes for a SARS-CoV-2 spike protein. The body then makes this protein, learns to recognize it, and makes immune cells to fight it so that it has a strengthened response if it encounters the virus.
In the cancer vaccine, the mRNA encodes for tumor-specific mutations called neoantigens. The body creates copies of these neoantigens, learns to recognize them, and creates more immune cells that can target them, therefore fighting the cancer.
The news is “very exciting,” Gritstone’s Allen says, “Up to this point, obviously we didn’t know that cancer vaccines could work. Essentially they have repeatedly failed for many years. And specifically, we didn’t know that they could work to augment the effects of checkpoint inhibitors. And both of those elements appear to have been proven now.”
Allen notes that Moderna and Merck have not released the full data from the trial. “But if we assume that what’s been reported publicly bears up to further scrutiny, then this is an important milestone for the field, obviously, and for us as a company.”
The Moderna-Merck cancer vaccine was only tested in patients with melanoma, and melanoma “is not typical,” Allen says. It has very high immunogenicity, he says, meaning it’s naturally able to elicit a strong immune response within the body that can hamper tumor progression, especially when that response is helped by activators like checkpoint inhibitors. Other cancer types spark a less powerful natural immune response, he says.
“The successes of melanoma don’t effortlessly translate into the more common solid tumors, like lung, colon, prostate, breast, and ovary, which are the big five,” he says.
Brown agreed that melanoma is different from other cancers and said that it has served as a proving ground for immunooncology agents. “But just because agents are successful there doesn’t preclude them from being successful in other tumor types,” she said.
Moderna and Merck plan to initiate a Phase 3 study in people with melanoma in 2023.