This audio is automatically generated. feedback.
As Merck & Co.’s blockbuster checkpoint inhibitor Keytruda approaches the 10th anniversary of its release, the pharmaceutical giant is seeking to lead the next wave of immunotherapy with a cancer vaccine in partnership with Moderna.
Dr. Scott Ebbinghaus, Vice President of Clinical Research at Merck
Used with permission from Merck
The development of the vaccine, called mRNA-4157, was a milestone event at the American Society of Clinical Oncology this year. result Mid-stage trials have shown that when combined with Keytruda, it improved survival rates for melanoma patients over three years.
Dr. Scott Ebbinghaus, Merck’s vice president of clinical research, said success in melanoma could pave the way for broader use of the vaccine in multiple tumor types, like its predecessor Keytruda, which currently has 39 indications in 17 different tumor types.
“What’s good about the three-year follow-up is that (the vaccine) showed very durable effects on recurrence-free survival and distant metastasis-free survival,” Ebbinghaus said. “This highlights the potential that this therapy has in melanoma, and we’re using melanoma as a precursor and proof of concept for expanding to other tumor types.”
The two drugs combined work in different ways to stimulate a patient’s immune system to attack cancer cells. Keytruda, a checkpoint inhibitor, releases the brakes on T cells, allowing them to attack tumors without being held back by disease defenses. The vaccine, also known as personalized neoantigen therapy, directs T cells to home in on tumors. Combining these approaches generates a stronger immune response.
“We have a drug that has the potential to help a lot of patients. I don’t know if we can really expect just one drug to have as broad an effect as Keytruda, but a combination of drugs could help just as many patients.”
Dr. Scott Ebbinghaus
Vice President, Clinical Research, Merck
The cancer vaccines are designed to precisely match a patient’s tumor antigens, using computer algorithms that sequence the cancer’s genome and predict the antigens that distinguish it from surrounding healthy cells.
In developing a vaccine, Expertise From Moderna, a COVID-19 vaccine innovator with which Merck is partnering Since 2016While cancer vaccines are not preventative, their treatment approach is very similar to how COVID vaccinations stimulate a response to the virus, and Ebbinghaus said the side effects are mild, especially as an oncology treatment.
Lessons from Keytruda
As late-stage clinical trials of the vaccine and Keytruda combination get underway, Ebbinghaus looks back at Merck’s long history in immuno-oncology, going back to a time when researchers weren’t sure whether the approach would work.
“In the ’80s and ’90s, there were always indications that immunotherapy might work against tumors like melanoma, kidney cancer and even some leukemias, but until Keytruda came along, people were pretty skeptical about whether it would work broadly,” Ebbinghaus says.
The early skepticism and eventual success taught Ebbinghaus and his team at Merck a lesson in perseverance, he said. Cancer vaccines have also been decades in the making, and only recently have they begun to show the clinical benefits scientists had hoped for.
Now, expectations are rising.
“We want to take the combination of[cancer vaccines and]Keytruda into the area of earlier disease,” Ebbinghaus said, “where immunotherapy may be most effective and where we can really use the word ‘cure.'”
And with Keytruda, the world’s top-selling drug in 2023, reaching its first patent expiration in a decade, the next wave of immunotherapy could mean change for both Merck and cancer patients. With more than 20 cancer drug candidates in late-stage clinical development, Merck is looking to diversify this time around, rather than focus on a flagship product like Keytruda, Ebbinghaus said.
“We have drugs that have the potential to help a lot of patients. We don’t know if one drug alone could have as broad an effect as Keytruda, but a combination of drugs could help just as many patients,” Ebbinghaus said.
Use a ready-made product
Merck and Moderna aren’t the only companies betting on personalized cancer vaccines: Moderna’s mRNA rival BioNTech, which partnered with Pfizer to develop the first COVID vaccine approved in the U.S., is conducting mid-stage trials for hard-to-treat cancers. Pancreatic cancer.
GritstoneBio is also employing a neoantigen approach to develop highly personalized treatments using a patient’s own tumor genome. Phase 2.
As these and other pharmaceutical companies pursue personalized treatment approaches, others are turning to off-the-shelf models that can be shared between patients and produced more quickly and at lower cost. Late-Stage Research It will also be used in combination with Merck’s Keytruda for melanoma patients.
Dr. Inge-Marie Svein, a cancer immunotherapy pioneer and co-founder of IO Biotech, said there will be room for both approaches once cancer vaccines become commercially available.
“Each approach has its pros and cons. Vaccines that target specific tumor antigens are very effective, but patients have to wait for them, and they’re not always possible for all patients,” Svein said. “Also, commercially available vaccines are available for a variety of cancer types, and this isn’t an either/or situation, they could work together.”
After decades of effort, cancer vaccine technology has made great strides in recent years because of leaps in researchers’ understanding of the immune system, Svaneh said.
“It was really naive to believe that you could just inject a protein and have an immune response and immediately create T cells,” Svein says, “but now that we understand so much better over the last decade, vaccines are a really good strategy, especially when combined with the checkpoint inhibitors that they’re built on.”
