Moderna and Merck announced positive results from a phase 3 trial for intismeran, an experimental personalised therapy against melanoma. According to the companies, an interim analysis of the INTerpath-001 study, which included 1,137 patients with high-risk cutaneous melanoma in stages IIB to IV completely removed by surgery, demonstrated that the combination of intismeran with Keytruda significantly improved recurrence-free survival in a statistically significant and clinically relevant manner compared to Keytruda alone. The treatment also improved distant metastasis-free survival.
Unlike preventive vaccines, intismeran is administered as a treatment after surgical removal of cancer to train the immune system to detect remaining tumour cells. The therapy is based on neoantigenens, proteins derived from specific mutations of each patient's tumour. The process begins with a tumour sample that is analysed to identify particular mutations, from which a synthetic mRNA is designed capable of encoding up to 34 neoantigenens selected for that specific cancer. Keytruda complements the strategy by blocking the PD-1 receptor, which can dampen the immune response.
According to Merck and Moderna, this is the first time that an individualised neoantigen therapy and an mRNA-based cancer treatment have delivered positive results in phase 3. In the previous phase 2b study, five-year follow-up showed a 49% lower risk of recurrence or death and a 59% lower risk of distant metastasis or death with the combination compared to Keytruda alone. The companies stress that those percentages correspond to the previous trial, not to the phase 3 recently disclosed.
Although the results achieved the primary endpoints, Merck and Moderna still need to present complete detailed data. The trial continues to evaluate other endpoints, including overall survival, and there is not yet an approved therapy. The companies plan to discuss a possible authorisation request with regulators and are already studying this strategy in other tumours, including non-small-cell lung cancer, bladder cancer and renal carcinoma.
