Cancer Vaccine Plus Keytruda Reduces Melanoma Recurrence or Death

Among patients with high-risk melanoma, median five-year follow-up data from the phase 2b KEYNOTE-942/mRNA-4157-P201 study showed that a combination of the individualized neoantigen therapy intismeran autogene plus Keytruda (pembrolizumab) continued to reduce the risk of recurrence or death compared to immunotherapy alone.

This pre-planned analysis focused on patients with stage 3/4 melanoma who had already undergone complete surgical resection to remove their tumors.

Main data that support the findings

In this latest long-term analysis, the combination of the personalized mRNA cancer vaccine intismeran autogene and the immunotherapy Keytruda demonstrated a sustained and clinically meaningful improvement in recurrence-free survival (RFS), which is the primary goal of the study. The data showed that the combination treatment reduced the risk of the cancer returning or the patient dying by 49% when compared to the group of patients who received only Keytruda.

The five-year results build upon previous findings released at the two-year and three-year follow-up marks. According to company leaders, these results highlight the potential for a prolonged benefit when using this individualized approach. The therapy is designed to address the significant risk of recurrence that remains for many patients with stage 3/4 melanoma, even after a successful surgery.

Trial details

The phase 2b KEYNOTE-942/mRNA-4157-P201 study is an ongoing randomized, open-label trial. It enrolled 157 patients with high-risk stage 3/4 melanoma who met specific eligibility criteria. These criteria required patients to have cutaneous melanoma that had spread to a lymph node and was at high risk of returning. All participating patients had to have a complete surgical resection within 13 weeks before receiving their first dose of Keytruda. Additionally, patients were required to be disease-free at the start of the study with no evidence of the cancer spreading to the brain.

Patients in the trial were assigned to one of two groups:

• The first group received 1 milligram of intismeran autogene every three weeks for nine doses, plus 200 milligrams of Keytruda every three weeks for up to 18 cycles (about one year).
• The second group received 200 milligrams of Keytruda alone for approximately one year.

The study tracks recurrence-free survival, which measures the time from the first dose until the cancer returns locally or in a distant part of the body, a new primary melanoma develops or the patient dies from any cause. Researchers also looked at secondary outcomes like distant metastasis-free survival and safety.

Intismeran autogene is a novel investigational messenger RNA (mRNA) therapy. It is individualized for each patient, consisting of synthetic mRNA that codes for up to 34 neoantigens. These neoantigens are identified based on the unique mutational signature of the DNA sequence of the patient's own tumor. This design is intended to train the body to generate specific T-cell responses based on that unique signature.

Because of these findings, a phase 3 study for melanoma is already fully enrolled. Other studies are currently enrolling patients with non-small cell lung cancer, renal cell carcinoma and bladder cancer to test the combination in different settings.

Safety of the treatment regimen

The safety of the treatment is a primary concern for patients and researchers. According to the announcement, the safety profile of the combination of intismeran autogene and Keytruda remained consistent with what had been reported in earlier stages of the study. During the trial, treatment continued for about one year or until the disease returned or the patient experienced unacceptable toxicity.

Reference

1. “Moderna & Merck Announce 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA® (pembrolizumab) Demonstrated Sustained Improvement in the Primary Endpoint of Recurrence-Free Survival in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection,” by Moderna & Merck. News release; Jan. 20, 2025.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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