Merck and Moderna have 'lot of exploring to do' after initial cancer vaccine success

Following Gary Keblish's diagnosis with melanoma in 2019, he underwent surgery to remove the tumor; however, this marked only the beginning of his journey, as melanoma can often recur aggressively post-surgery. Subsequently, Keblish was enrolled in a clinical trial for the personalized mRNA cancer vaccine developed by Merck and Moderna.

In a video appearance at the STAT Summit on Thursday, Keblish illustrated his experience with the ups and downs of his treatment, likening it to a ride on Ms. Frizzle's Magic School Bus. "Seatbelts, everyone!," he remarked, expressing gratitude for the chance to participate in the trial.

Today, he continues his role as a teacher while Merck and Moderna prepare to submit their vaccine for regulatory approval, following their announcement in August that the vaccine significantly delayed cancer recurrence and the onset of metastatic disease in melanoma patients like Keblish during a substantial Phase 3 trial.

This development marks a pivotal milestone in the field of cancer vaccines, which has historically faced challenges in delivering on its promises. Nevertheless, the work of both companies is far from finished. They are now focused on demonstrating that the vaccine is not solely effective for melanoma patients but has the potential to impact a wider range of tumors, similar to earlier generations of immunotherapies.

The path forward is one of careful research and significant investment.

Moderna's President Stephen Hoge noted the need for strategic exploration, emphasizing, "We have a lot of exploring to do and need to prioritize where we explore," during his presentation at the summit.

Alongside Hoge, Dean Li, the R&D chief at Merck, detailed their exploration strategy. The vaccine, referred to chemically as intismeran autogene, is designed to work in conjunction with Merck's prominent immunotherapy, Keytruda, which has been evaluated in thousands of trials over the past 15 years. Keytruda has been observed to perform better on certain tumors—known as "hot tumors" that typically exhibit numerous mutations—compared to other tumor types classified as "cold."

Li remarked, "We know exactly where I-O [immuno-oncology] works, where a checkpoint inhibitor works, where it doesn't, where it almost worked and didn't make it."

Thus far, their research has honed in on situations where Keytruda has demonstrated optimal effectiveness, such as being utilized as an adjuvant—an auxiliary treatment—for melanoma patients who have undergone surgical removal of visible tumors. Currently, they are conducting trials on adjuvant lung, kidney, and bladder cancers.

Li and Hoge expressed potential avenues for exploration, which could involve tumors where Keytruda has not succeeded but where alternative immunotherapies have shown promise, or employing the vaccine as a standalone treatment for early-stage tumors. Hoge stated, "There's an incredible opportunity to think about how we bring immunotherapy into earlier interventions and really intercept cancer so that we don't present with stage three, stage four disease later."

Li contrasted their method with that of "other people" who "may not have the advantage" of their level of expertise and have opted to pursue cold or metastatic tumors—implicitly referencing Moderna's competitor, BioNTech, which has had some promising but also challenging outcomes.

Li stated, "We have chosen not to do this. But I can tell you: Anyone has positive data and it's out there, you will never see Moderna and Merck pivot [so] fast."

Small-scale trials for adjuvant pancreatic and gastric cancers are currently in progress to explore this potential, while Li also mentioned the possibility of employing the vaccine in patients whose metastatic tumors have been reduced through alternative therapies.

Simultaneously, the companies are seeking to enhance the technology behind their vaccine. It is created by analyzing individual tumors and deploying an algorithm to identify up to 34 mutant proteins, with the expectation that these proteins can serve as a "wanted sign" for the immune system.

While the algorithm presents challenges, careful analysis of the immune responses in trial participants could enable Merck and Moderna to develop even more effective algorithms in the future.

"It's a real privilege to have all that information across the now several thousand people in our phase three program," Hoge concluded. "I'm looking forward to digging into it."