- A Moderna personalized cancer vaccine combined with Merck & Co.’s immunotherapy Keytruda kept people with melanoma alive and disease free after surgery significantly longer than Keytruda alone in a mid-stage trial, the companies said Tuesday.
- It was the first major finding for one of Moderna’s non-COVID vaccines, which was a focus for its investors before the pandemic began in 2020. The companies said they hope to get a Phase 3 trial underway in 2023 and will begin testing the combination in other types of cancer.
- In October, Merck paid $250 million to license the Moderna vaccine, for which it had originally signed an option in 2016. Combination therapies are one way that Merck could help stave off biosimilar competition to Keytruda when the drug’s main patent expires in 2028.
Melanoma was the first type of cancer for which Keytruda gained FDA approval because of its sensitivity to attack from immune cells. Moderna’s personalized cancer vaccine, called mRNA-4157/V940, is derived from patient tissue samples. The company uses them to identify tumor cell mutations, which are then used to design a messenger RNA vaccine that will spur a T cell response specific to the patient’s cancer.
The combination trial was in the “adjuvant” setting, in which patients first undergo surgical removal of tumors and then undergo treatment to keep cancer from returning.
Keytruda and Bristol Myers Squibb’s rival drug Opdivo are both already approved in the adjuvant setting. In testing, Merck’s drug reduced the risk of death or recurrence by 43% when compared to placebo after surgery, while Opdivo reduced these risks by 35% when compared to another melanoma immunotherapy called Yervoy.
In Moderna’s Phase 2b trial, MRNA-4157/V940 with Keytruda reduced the risk of death or recurrence by 44% over Keytruda alone, a statistically significant finding that will need to be confirmed in Phase 3 study. The trial was in 157 patients, and didn’t mask researchers or patients from knowing whether they received the Moderna vaccine.
The companies said they will begin discussing with the Food and Drug Administration the design of a Phase 3 trial, which will likely need to be at least the size of the Keytruda adjuvant melanoma trial, which had 976 particiapnts. It could also need a placebo control to conceal which patients receive the Moderna vaccine.
The results raised hopes Moderna’s personalized cancer vaccine approach could build on the success Merck, Bristol Myers and other drugmakers have had in developing so-called checkpoint inhibitors that impede cancers’ mechanism to evade immune attack.
Since its first approval in melanoma, Keytruda has expanded into 17 other types of cancer, including some in which the tumor has a specific mutational signature regardless of what organ it is located in.
“While the opportunity in the studied adjuvant setting is modest in absolute terms, demonstrating added benefit represents clinical proof of concept for [personalized cancer vaccines], with potential read-across to other oncology indications,” SVB Securities analyst Mani Foroohar wrote in a note to clients.
Other companies working with similar vaccines are Moderna’s COVID-19 rival BioNTech, partnered with Roche, Gritstone Bio and Nykode Therapeutics.
Moderna shares rose 23% in morning trading.