Biopharmaceutical companies Moderna Inc. (NASDAQ:MRNA) and Merck & Co., Inc. (NYSE:MRK) have reported updated results from the median five-year follow-up of their Phase 2b clinical trial assessing an innovative mRNA-based individualized neoantigen therapy for high-risk melanoma patients. This research centers on the combination of intismeran autogene (mRNA-4157 or V940) and Merck's PD-1 inhibitor, Keytruda (pembrolizumab), administered as an adjuvant treatment following complete surgical removal of stage III or IV melanoma.
The study, known by its designation KEYNOTE-942/mRNA-4157-P201, evaluates the durability of treatment benefits in a population where melanoma recurrence risk is significant despite resection. According to the pre-planned analysis, the combination therapy offers a meaningful survival advantage measured by the primary endpoint of recurrence-free survival (RFS). Specifically, patients receiving intismeran autogene alongside Keytruda demonstrated a 49% reduction in the risk of either melanoma returning or death occurring compared with those treated with Keytruda as a monotherapy.
This positive outcome extends findings from earlier analyses performed around two and three years into the trial, confirming the sustained efficacy of the combined approach. Furthermore, the safety profile observed to date aligns with prior data and does not raise new concerns regarding tolerability.
Moderna and Merck are preparing to share additional insights from ongoing assessments of both primary and secondary endpoints at an upcoming medical conference. These comprehensive analyses promise to elucidate further the long-term clinical benefits and safety outcomes associated with this treatment strategy.
In parallel efforts, Moderna and Merck have fully enrolled patients in the INTerpath-001 Phase 3 clinical trial, which investigates this mRNA vaccine's impact in the adjuvant melanoma setting. They are also advancing two Phase 3 studies addressing adjuvant therapy in non-small cell lung cancer (NSCLC); these evaluate treatments post-complete surgical resection and following neoadjuvant administration of Keytruda combined with platinum-based chemotherapy.
Broadening their immuno-oncology portfolio, the companies report full enrollment in a Phase 2 trial investigating intismeran autogene as adjuvant therapy for renal cell carcinoma. Recruitment is ongoing for randomized Phase 2 studies targeting resected muscle-invasive bladder cancer and non-muscle-invasive bladder cancer, as well as first-line treatments for patients with metastatic melanoma and metastatic squamous NSCLC.
Industry analysts have responded positively to the five-year findings. William Blair noted that though the data represent an incremental update, they reinforce the notable survival benefit of intismeran over Keytruda alone, highlighting this combination as a pioneering post-surgical therapy that provides added advantage. Analyst Myles Minter emphasized that these long-term data are consistent with prior RFS analyses, suggesting the adaptive immune responses elicited by intismeran largely predict effective tumor control in patients.
On the market side, Moderna’s shares experienced an uptick following the news, closing at $43.00 on Tuesday afternoon, reflecting investor confidence in the therapy's sustained impact for melanoma patients.