By Julie Steenhuysen and Michael Erman
CHICAGO (Reuters) – An experimental personalized melanoma vaccine developed by Moderna Inc given with Merck & Co’s blockbuster immunotherapy Keytruda cut the risk of the skin cancer’s recurrence or death by 44% compared with Keytruda alone in a midstage trial.
The study is the first randomized trial to show that combining mRNA vaccine technology – which has been behind the development of successful COVID-19 vaccines – with a drug that revs up the immune response would offer a better result for patients with the most deadly type of skin cancer.
The companies hailed the results as spectacular.
“It’s a tremendous step forward in immunotherapy,” Eliav Barr, Merck’s head of global clinical development and chief medical officer, said in an interview.
Paul Burton, Moderna’s chief medical officer, said in a separate interview the combination “has the capacity to be a new paradigm in the treatment of cancer.”
The ongoing study involved 157 patients with stage III/IV melanoma whose tumors were surgically removed before being treated with the drug/vaccine combo or Keytruda alone with the aim of delaying disease recurrence.
The combination was generally safe and showed a statistically significant benefit compared with Keytruda alone after a year of treatment. Serious drug-related side effects occurred in 14.4% of patients who received the drug-vaccine combination compared with 10% with Keytruda alone.
A PROMISING FIELD
In October, Merck exercised an option to jointly develop and commercialize the treatment, known as mRNA-4157/V940, sharing costs and any profits equally. Merck and Moderna plan to discuss the results with regulatory authorities and start a phase 3 study in melanoma patients in 2023.
The Merck/Moderna collaboration is one of several combining powerful drugs that unleash the immune system to target cancers with mRNA vaccine technology. These so-called neoadjuvant vaccines are designed to target highly mutated tumors.
The personalized vaccine works in concert with Merck’s Keytruda, a so-called checkpoint inhibitor designed to disable a protein called programmed death 1, or PD-1, that helps tumors to evade the immune system.
To build the vaccine, researchers took samples of patients’ tumors and healthy tissue. After analyzing the samples to decode their genetic sequence and isolate mutant proteins associated only with the cancer, that information was used to design a tailor-made cancer vaccine.
When injected into a patient, the patient’s cells act as a manufacturing plant, producing perfect copies of the mutations for the immune system to recognize and destroy.
Moderna’s personalized vaccine can be made in about eight weeks, a timeframe the company eventually hopes to cut in half, Burton said. Assuming the combination is eventually approved, he said Moderna would need to do a “massive scale-up” of its manufacturing capabilities and that company is “all in”.
Barr said the companies intend to study the approach in other types of highly mutated cancers, such as lung cancer. Other highly mutated cancers include bladder cancers and some triple negative breast cancers.
Moderna mRNA competitor BioNTech SE likewise has several cancer vaccine trials in the works including one with Memorial Sloan Kettering Cancer Center in New York, which is testing a personalized BioNTech vaccine in combination with Roche’s Tecentriq in patients with pancreatic cancer.
Gritstone Bio Inc is testing a personalized, self-amplifying mRNA vaccine in combination with Bristol Myers Squibb’s immunotherapies Opdivo and Yervoy in a midstage trial in patients with advanced solid tumors.
Experts said the personalized vaccines were among several promising cancer vaccine ideas in the works after many failures in the field.
“In general, I think cancer vaccines are kind of at a tipping point, and there are going to probably be a lot of vaccines coming down the pipeline in the next five years,” said Dr. Mary Lenora Disis, director of the UW Medicine Cancer Vaccine Institute in Seattle.
Although the COVID-19 pandemic demonstrated the speed, ease and safety of mRNA vaccines, they came out of years of cancer vaccine research, she said. “When COVID came, they were able to easily pivot.”
(Reporting by Julie Steenhuysen and Michael Erman; Editing by Caroline Humer, Bill Berkrot and Edwina Gibbs)
