A personalized mRNA cancer therapy developed by Moderna and Merck outperformed Keytruda alone in a phase 3 clinical trial involving patients with high-risk melanoma, the companies announced August 19. The experimental treatment, called intismeran, met its primary endpoint of recurrence-free survival as well as a key secondary endpoint measuring distant metastasis-free survival, according to reporting by Healthline.
Recurrence-free survival measures whether cancer returns or a patient dies. Distant metastasis-free survival tracks how long it takes for cancer to spread to another part of the body, or for death to occur. The trial showed the combination of intismeran and Keytruda performed better than Keytruda alone on both measures.
Intismeran is a custom-made vaccine built specifically for each individual patient. It uses messenger RNA technology to encode up to 34 patient-specific neoantigens, which are proteins produced by the unique mutations in a patient's tumor. The vaccine is designed to train the immune system's T cells to recognize and attack those specific cancer cells. Keytruda, a PD-1 checkpoint inhibitor, works by releasing the immune system's natural brakes so it can better detect and fight cancer. Together, the two treatments work in complementary ways: Keytruda releases the brakes, and intismeran gives the immune system directions to find the cancer.
Georgina Long, Medical Director of Melanoma Institute Australia and the study's principal investigator, described the results as a turning point. "Today's results represent a landmark moment for adjuvant melanoma treatment," she said in a press release. "This is the first Phase 3 study to show that intismeran, a treatment designed based on the unique mutational 'fingerprint' of a patient's own tumor, given in combination with pembrolizumab, can reduce the risk of recurrence or death in patients with completely resected stage IIB-IV melanoma compared to KEYTRUDA alone."
Earlier phase 2b results had shown that intismeran plus Keytruda was associated with a 49% lower risk of melanoma recurrence or death and a 59% lower risk of distant metastasis or death compared with Keytruda alone. The phase 3 results are consistent with that earlier signal, though the companies have not yet released detailed efficacy or safety data from the newer trial.
Intismeran remains investigational and has not been approved by the Food and Drug Administration. Moderna and Merck said they plan to submit findings to regulatory authorities and present full results at an upcoming medical meeting. The phase 3 trial is still ongoing.
Experts have noted that while the results are encouraging, detailed data are still needed before the full scope of the treatment's benefits and safety profile can be understood. The trial involved patients with completely resected stage IIB through stage IV melanoma, meaning patients whose tumors had been surgically removed but who remained at high risk for recurrence.
