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Adding mRNA-4157, a personalized cancer vaccine, to treatment with pembrolizumab improves recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with high-risk, resected melanoma, a phase 2 trial suggests.
At a median follow-up of about 2 years, mRNA-4157 and pembrolizumab yielded a 44% reduction in the risk of recurrence or death and a 65% reduction in distant metastasis or death over pembrolizumab alone, said Adnan Khattak, PhD, of Hollywood Private Hospital and Edith Cowan University in Perth, Australia.
Dr Khattak reported these results, from the KEYNOTE-942 trial, at the ASCO Annual Meeting 2023.
The trial (ClinicalTrials.gov Identifier: NCT03897881) included 157 patients with resected, stage IIIB-IV cutaneous melanoma at a high risk of recurrence. The patients were randomly assigned to receive pembrolizumab monotherapy (n=50) or the combination of mRNA-4157 and pembrolizumab (n=107).
The patients had undergone complete resection no more than 13 weeks prior to their first pembrolizumab dose and were free of disease at study entry. Baseline characteristics were well balanced between the treatment arms.
In both arms, pembrolizumab treatment continued for up to 1 year (200 mg every 3 weeks for up to 18 cycles). In the combination arm, patients also received mRNA-4157 as a 1 mg intramuscular injection every 3 weeks for up to 9 doses.
The median follow-up was 23 months for the combination arm and 24 months for monotherapy arm.
Patients in the mRNA-4157 arm had a significantly lower risk of relapse or death than patients in the pembrolizumab monotherapy arm (hazard ratio [HR], 0.561; 95% CI, 0.309-1.017; P =.0266).
The 1-year RFS rate was 83.4% in the mRNA-4157 arm and 77.1% in the monotherapy arm. The 18-month RFS rates were 78.6% and 62.2%, respectively.
Patients in the mRNA-4157 arm also had a significantly lower risk of distant metastasis or death than patients in the monotherapy arm (HR, 0.347; 95% CI, 0.145-0.828; P =.0063). The 18-month DMFS rates were 91.8% and 76.8%, respectively.
The mRNA-4157 vaccine was not associated with an increase in immune-mediated toxicity, Dr Khattak noted.
All patients in the mRNA-4157 arm experienced treatment-related adverse events (TRAEs), compared to 82% of patients in the pembrolizumab monotherapy arm. Grade 3 or higher TRAEs were seen in 25% and 18% of patients, respectively.
The most common TRAEs related to mRNA-4157 or the combination were fatigue (60.6%), injection site pain (55.8%), and chills (50.0%).
This study is the first randomized trial showing improved RFS and DMFS for an individualized neoantigen treatment approach, Dr Khattak said. He noted that the US Food and Drug Administration granted mRNA-4157 plus pembrolizumab breakthrough therapy designation in February of this year.
Disclosures: This research was supported by Moderna. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Khattak A, Weber JS, Meniawy T, et al. Distant metastasis-free survival results from the randomized, phase 2 mRNA-4157-P201/KEYNOTE-942 trial. ASCO 2023. June 2-6, 2023. Abstract LBA9503.
This article originally appeared on Cancer Therapy Advisor
