Personalized cancer vaccines are getting closer to market. Merck and Moderna just showed successful manufacturing in a large Phase 3 trial, proving they can deliver the goods.
Personalized cancer vaccines are getting closer to market after Merck and Moderna showed that their mRNA shot–Keytruda combo for melanoma reduced the risk of death or recurrence at a drama-filled showing during last month’s European Society of Medical Oncology (ESMO) Congress.
But these vaccines aren’t like a flu shot—they are custom-made for the patient using samples from their unique tumors obtained during resection—so the companies also had to show that they will be able to deliver the product as needed to patients.
“Ultimately, if you have a drug like this, you want to make sure you can deploy it around the world and you can give patients this benefit consistently,” Jane Healy, Merck’s head of oncology early clinical development, told BioSpace ahead of the presentation in Spain.
In the Phase 3 INTerpath-001 trial, the mRNA vaccine intismeran autogene, paired with Merck’s mega-blockbuster Keytruda, reduced risk of recurrence or death by 42%, with a hazard ratio of 0.58 in patients with resected stage 2b to 4 melanoma. The study included 1,137 patients.
Merck also reported that the drug was successfully manufactured during the trial. Healy said that 99% of patients in the vaccine treatment arm were able to receive a manufactured vaccine, matching earlier results from the much smaller Phase 1 and 2 trials.
“We’re able to get this to patients around the world,” Healy said. The study was conducted in the U.S., South America, Australia, Europe, the U.K., Canada, the Middle East, South Africa and Asia, according to ClinicalTrials.gov.
Making the individualized neoantigen therapy (INT) is an involved process. Patient tumor tissue obtained during resection is sequenced to identify the specific mutational signature of the cancer, then a personalized synthetic mRNA code is written for up to 34 neoantigens. That code tells the immune system how to fight the unique cancer. Ideally, patients get the full 34 neoantigens but they can also see benefit from fewer, Healy noted.
“You need to have sufficient tissue in order for you to be able to run the sequencing analysis to then make the design of the INT, which can then subsequently be manufactured,” she explained.
Merck found that 82% of patients screened for the trial had enough tissue. Of those, 91% went on to get the full neoantigen range out of their samples while the remaining patients had fewer neoantigens but still successful manufacture, bringing the full number up to 99% of patients in the treatment arm. Healy said those that did not get the 34 total neoantigens were still very close to the highest level.
“Overall, the manufacture process is very successful, and in most cases, in patients that have melanoma that is being surgically receptive, they have sufficient tissue to make the vaccine,” Healy said.
Melanoma is just the beginning for intismeran. Merck and Moderna are also running trials in renal cell carcinoma, non-small cell lung cancer, bladder cancer and other types of melanoma. But this initial indication has helped the partners achieve proof of concept for the manufacturing.
“It’s both a conducive setting for the success of this [and] the experience we had on the trial showed that we can do it consistently,” Healy said.
