ctDNA Patterns May Predict Outcomes Achieved With mRNA-4157 Plus Pembrolizumab in High-Risk Melanoma
Source: OncLive, January 2024
The addition of a personalized mRNA vaccine to standard-of-care (SOC) pembrolizumab (Keytruda) improved survival outcomes vs pembrolizumab alone in resected high-risk melanoma, and monitoring ctDNA patterns over time can provide valuable insights into the degree of benefit patients can expect to achieve from the approach, according to Jeffrey S. Weber, MD, PhD.
Findings from the phase 2b mRNA-4157-P201/KEYNOTE-942 trial (NCT03897881) of mRNA-4157 (V940) plus pembrolizumab in patients with stage IIIB, IIIC, IIID, or IV cutaneous melanoma were presented at the2023 ESMO Congress. Patients treated with the combination experienced a statistically significant and clinically meaningful improvement in recurrence-free survival (RFS; HR, 0.561; 95% CI, 0.309-1.017; P = .0266) and distant metastasis-free survival (DMFS; HR, 0.347; 95% CI, 0.145-0.828; P = .0063) vs pembrolizumab alone. Notably, higher recurrence rates were observed in molecular nonresponders vs molecular responders; this suggests that ctDNA positivity at baseline or later in the treatment course may serve as a negative prognostic factor for clinical outcomes with the combination.
“KEYNOTE-942 in its initial iteration has a clear signal of efficacy for the combination vs pembrolizumab alone,” said Weber, who serves as the deputy director of the New York University (NYU) Perlmutter Cancer Center, co-director of the Melanoma Research Program, and a Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at the NYU Grossman School of Medicine. “We’re going to see many patients on neoantigen vaccine trials in the next couple of years, and this [approach may] change the face of oncology.”