According to results from the mRNA-4157-P201/KEYNOTE-942 trial, the novel cancer vaccine mRNA-4157 in combination with adjuvant pembrolizumab, significantly prolonged distant metastasis-free survival (DMFS) among patients with resected high-risk melanoma, when compared to pembrolizumab alone.

Data were presented by lead study author Adnan Khattak, MBBS, PhD, FRACP, MBBS, One Clinical Research and Edith Cowan University, Perth, Western Australia, Australia, at the 2023 ASCO Annual Meeting. 

mRNA-4157 is a novel mRNA-based personalized cancer vaccine which encodes up to 34 patient-specific tumor neoantigens. As previously reported the mRNA-4157-P201/Keynote-942 trial met its primary endpoint of recurrence free survival (RFS) among patients with resected high-risk stage 3B/C/D and 4 melanoma. The current study reports on the first analysis of secondary efficacy end points.

In this open label, phase 2 trial, a total of 157 pPatients were randomized on a 2-to-1 ratio (stratified by stage) to either receive either pembrolizumab in combination with mRNA-4157 (n = 107) or pembrolizumab alone (n = 50). In the combination arm, patients received 1 mg of mRNA-4157 every 3 weeks for a total of 9 doses, plus 200 mg pembrolizumab every 3 weeks for up to 18 cycles. The secondary end point reported in this analysis is of distant metastasis-free survival, as was pre-specified and hierarchically tested following positive RFS.

There was a statistically and clinically significant improvement seen in DMFS for those patients in the combination arm vs the pembrolizumab monotherapy arm (hazard ratio [HR], .347; 95% CI, 0.145 to 0.828; 1-sided P-value = .0063). The 18-month DMFS rates were  91.8% vs 76.8% in the combination and monotherapy arm, respectively. Distant recurrence or death was reported in 8.4% of patients in the combination arm and 24% of patients in the monotherapy arm.

Dr Khattak et al concluded, “These results also provide further evidence that a personalized neoantigen approach is potentially beneficial for cancer patients,” adding that a phase 3, randomized study of this regimen for patients with melanoma is forthcoming.

Source:

Khattak A, Weber J, Meniawy T, et al. Distant metastasis-free survival results from the randomized, phase 2 mRNA-4157-P201/KEYNOTE-942 trial. Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract LBA9503