Moderna and Merck’s Cancer Vaccine Cuts Risk of Recurrence or Death 44% in Late-Stage, High-Risk Melanoma After Resection

Patients with stage III or IV melanoma who were at high risk or recurrence who received an investigational therapeutic cancer vaccine following complete resection saw a 44% reduced likelihood of recurrence compared with patients treated with pembrolizumab alone, according to results presented Sunday at the American Association of Cancer Research (AACR). Results were announced by the companies in a news release.

In the overall intention-to-treat population, adjuvant treatment with mRNA-4157 and pembrolizumab resulted in a hazard ratio (HR) of 0.56 (95% CI, 0.309-1.017); one-sided P value = 0.0266) compared with pembrolizumab alone.

The novel treatment, which combines messenger RNA (mRNA-4157) individualized neoantigen therapy with the PD-1 inhibitor pembrolizumab, allowed 78.6% (95% CI, 69.0%-85.6) of the patients to achieve recurrence-free survival (RFS) at 18 months compared with 62.2% (95% CI, 46.9%-74.3%) of those in the pembrolizumab arm. A statement from AACR said the benefit was seen regardless of tumor mutational burden (TMB) status, according to results from the phase 2b trial presented during the meeting.

“Today’s results provide further encouragement for the potential of mRNA as an individualized neoantigen therapy to positively impact patients with high-risk resected melanoma,” Kyle Holen, MD, Moderna's senior vice president and head of development, Therapeutics and Oncology, said in the statement. “The profound observed reduction in the risk of recurrence-free survival suggests this combination may be a novel means of potentially extending the lives of patients with high-risk melanoma. We look forward to starting the phase 3 melanoma trial soon and expanding testing to lung cancer and beyond.”

Barr

“Data from KEYNOTE-942 provide evidence for the potential of mRNA-4157 (V940) in combination with KEYTRUDA to improve recurrence-free survival when given to patients with resected high-risk melanoma,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said in the news release.

Barr said the data show the potential benefits of the investigational mRNA neoantigen therapy with pembrolizumab in treating melanoma earlier. Not only does Merck look forward to the phase 3 study in melanoma, he said; there is potential for its use it other early stage cancers.

This Merck/Moderna collaboration is one of several exploring the use of therapeutic cancer vaccines. Merck’s pembrolizumab is being studied with other vaccine delivery systems, including IMV Inc.’s DPX technology in diffuse large B-cell lymphoma and bladder cancer.

The FDA and the European Medicines Agency has already granted Breakthrough Therapy Designation for mRNA-4157 in combination with pembrolizumab in the adjuvant setting for patients with high-risk melanoma following complete resection.

Reference

Khattak A, Carlino M, Meniawy T, et al. A personalized cancer vaccine, mRNA-4157, combined with pembrolizumab versus pembrolizumab in patients with resected high-risk melanoma: Efficacy and safety results from the randomized, open-label Phase 2 mRNA-4157-P201/Keynote-942 trial. Presented at: 2023 AACR Annual Meeting; April 14-19, 2023; Orlando, FL. Abstract CT001.