Moderna and Merck Report 5-Year Data for Melanoma Cancer Vaccine Intismeran Autogene

Moderna and Merck announced median five-year follow-up data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study, evaluating intismeran autogene (mRNA-4157 or V940), an investigational mRNA-based individualized neoantigen therapy, in combination with Keytruda (pembrolizumab) in patients with high-risk melanoma (stage III/IV) following complete resection. In this pre-planned analysis, adjuvant treatment with intismeran autogene in combination with Keytruda continued to demonstrate sustained and clinically meaningful improvement in the study's primary endpoint, recurrence-free survival, reducing the risk of recurrence or death by 49% (HR=0.510; [95% CI, 0.294–0.887]; one-sided nominal p=0.0075) compared to Keytruda alone.

The Phase 2b KEYNOTE-942 study is an ongoing randomized, open-label trial that enrolled 157 patients with high-risk stage III/IV melanoma. Following complete surgical resection, patients were assigned 2:1 (stratified by stage) to receive intismeran autogene (1 mg every three weeks for nine doses) and Keytruda (200 mg every three weeks up to 18 cycles [for approximately one year]) versus Keytruda alone. This analysis builds on the primary analysis conducted at approximately two years of follow up, as well as a subsequent analysis at three years of follow up. The safety profile of intismeran autogene in combination with Keytruda in the study remains consistent with that previously reported.

Moderna and Merck plan to present further data from follow up analyses of primary and secondary endpoints at an upcoming medical meeting. The companies are advancing intismeran autogene through multiple clinical trials across various tumor types. In collaboration with Merck, the Phase 3 clinical trial for adjuvant melanoma (INTerpath-001, NCT05933577) is fully enrolled. Two non-small cell lung cancer Phase 3 studies, evaluating adjuvant treatment in patients with completely resected NSCLC and evaluating adjuvant treatment for patients with resectable NSCLC after receiving neoadjuvant Keytruda plus platinum-based chemotherapy, are enrolling.

The randomized Phase 2 study for adjuvant renal cell carcinoma is fully enrolled. Randomized Phase 2 studies for patients with resected muscle invasive and resected non-muscle invasive bladder cancer are enrolling, a Phase 2 study of first-line treatment for patients with metastatic melanoma and a Phase 2 study of first-line treatment for patients with metastatic squamous NSCLC are also enrolling.

Intismeran autogene is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy consisting of a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity. Individualized neoantigen therapies are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient's tumor.

In partnership with Moderna, Merck is developing intismeran autogene in combination with Keytruda in pivotal phase III studies for earlier-stage and adjuvant NSCLC and adjuvant melanoma. Keytruda, approved for several types of cancer, accounts for around 55% of Merck's pharmaceutical sales. Keytruda recorded sales of $31.7 billion in 2025, up 7% year over year. Keytruda is set to lose patent exclusivity post-2028, with Merck expecting the drug to achieve peak sales of $35 billion by 2028.