Merck's 3-Part Cancer Strategy Post-Keytruda Features Moderna Vaccine

Merck & Co. is steering its oncology research and development strategy towards three key initiatives, with a significant spotlight on the Moderna-shared cancer vaccine, mRNA-4157, amidst the impending 2028 patent expiration of their blockbuster drug, Keytruda. Eliav Barr, M.D., Merck’s senior vice president and head of global clinical development, shared insights into this strategy at the American Society of Clinical Oncology (ASCO) conference in Chicago.

The revised R&D approach comprises three pillars. The first aims to enhance immune responses to cancer, prominently featuring the mRNA-4157 vaccine. This asset, developed in collaboration with Moderna, is used in combination with Keytruda to amplify the immune system's response against cancer. Barr highlighted the profound shift in the perception of cancer vaccines, which once were regarded with skepticism but now usher in new possibilities.

During the ASCO event, Merck and Moderna showcased promising three-year data from a phase 2b trial (KEYNOTE-942) involving mRNA-4157 combined with Keytruda for resected, high-risk melanoma patients (stage 3/4). The trial included 157 patients who had undergone complete tumor resection. The results indicated that the combination therapy reduced the risk of cancer recurrence or death by 49% compared to Keytruda alone, marking an improvement from the previously reported 44% recurrence-free survival rate at the two-year follow-up.

Barr emphasized the significance of these findings, noting that they demonstrate robust and persistent efficacy, critical for long-term tumor control. The vaccine aims to reset the immune system to mount a vigorous anti-tumor response, and thus far, the data has shown sustained benefits without late relapses, which would suggest the vaccine's initial effectiveness diminishes over time.

However, the combination therapy did show a marginally higher incidence of adverse events compared to Keytruda alone. Immune-related adverse events were reported in 37.5% of patients receiving the combination, compared to 36% with Keytruda alone. Common side effects included fatigue and injection site pain, mostly mild to moderate in severity. Barr remarked that the adverse events were manageable and did not necessitate restrictions on patient populations who might benefit from the therapy.

Merck and Moderna are accelerating patient enrollment for a phase 3 trial of the vaccine-Keytruda combo in high-risk melanoma, targeting 1,089 participants with a completion date projected for October 2029. Barr acknowledged that the pioneering nature of this cancer vaccine would invite rigorous regulatory scrutiny, especially as it represents a novel class of intervention. The breakthrough designation granted to mRNA-4157 in February 2023 facilitates ongoing dialogue with the FDA, helping Merck and Moderna align with regulatory expectations.

Beyond boosting immune responses, Merck’s second strategic pillar focuses on targeting chemotherapy and other cancer-eliminating treatments directly to tumors. The third pillar emphasizes precision targeting therapies designed to address specific genetic mutations that drive tumor development. These multifaceted approaches underscore Merck’s commitment to evolving its oncology pipeline to meet future challenges in cancer treatment and maintain its leadership in the field.