Study results showed KEYTRUDA significantly prolonged recurrence-free survival (RFS), reducing the risk of disease recurrence or death by 43% compared to placebo in the overall study population (HR=0.57 [98.4% CI, 0.43-0.74]; p<0.0001).
For the primary endpoint of RFS in the overall study population, the one-year RFS rate was 75.4 percent (95% CI, 71.3-78.9) for KEYTRUDA compared to 61.0 percent (95% CI, 56.5-65.1) for placebo.
For the co-primary endpoint of RFS in patients whose tumors were considered PD-L1 positive, KEYTRUDA demonstrated significantly prolonged RFS compared to placebo (HR=0.54; 95% CI, 0.42-0.69; p<0.0001). The safety profile of KEYTRUDA was consistent with what has been seen in previous trials among patients with advanced melanoma.
These results are being presented today for the first time in the opening plenary session at the American Association for Cancer Research (AACR) Annual Meeting 2018 (Abstract #10526), with simultaneous publication in The New England Journal of Medicine.
Merck Research Laboratories global clinical development head and senior vice president Dr Roy Baynes said: “These data demonstrate compelling evidence that adjuvant treatment with KEYTRUDA provides significant recurrence-free survival benefit after surgery in patients with high-risk Stage III melanoma.
“These are the first data for KEYTRUDA in the adjuvant setting and mark an important advancement for the treatment of resected stage III melanoma. We are pleased to be sharing these data with global regulatory authorities.”
KEYTRUDA is the first anti-PD-1 therapy to show RFS benefit across stage IIIA (> 1 mm lymph node metastasis), IIIB and IIIC melanoma. The RFS benefit was also seen regardless of BRAF mutation status (HR=0.64 [99% CI, 0.42-0.96] for patients with wild-type BRAF status; HR=0.57 [99% CI, 0.37-0.89] for patients with mutant BRAF status).
As previously announced, Merck is working to submit data from EORTC1325/KEYNOTE-054 to regulatory agencies in the U.S. and around the world.
“As an organization dedicated to eliminating melanoma suffering and death, we are thrilled to see these important new data on KEYTRUDA,” said Louise M. Perkins, Ph.D., chief science officer, Melanoma Research Alliance.
“The ability to significantly prevent melanoma from coming back after surgery, along with a demonstrated safety profile, makes this a welcome development in the fight against melanoma.”
Merck has a broad clinical development program in melanoma with KEYTRUDA as monotherapy and in combination with other novel mechanisms.
The program, which is comprised of more than 4,500 patients across 10 clinical studies, is evaluating KEYTRUDA across all settings and stages of the disease.
EORTC 1325/KEYNOTE-054 is a randomized, double-blind, Phase 3 study (ClinicalTrials.gov, NCT02362594) sponsored by Merck and conducted in collaboration with the EORTC. The study is evaluating adjuvant therapy with KEYTRUDA compared to placebo in patients with resected high-risk melanoma (stage IIIA [> 1 mm lymph node metastasis], IIIB and IIIC).
In total, the study enrolled 1,019 patients who were randomly assigned to receive either an intravenous infusion of KEYTRUDA 200 mg (n=514) or placebo (n=505) every three weeks for up to 1 year (a total of 18 doses). Upon documented recurrence, patients were eligible for cross-over/re-challenge with KEYTRUDA.
Co-primary endpoints were RFS for all patients and RFS in patients whose tumors express PD-L1; secondary endpoints include distant metastases-free survival and overall survival (OS) in all patients and in patients whose tumors express PD-L1.
RFS was defined as the time from randomization until the date of first recurrence (local, regional or distant metastasis) or death from any cause.
In accordance with the trial protocol, the study is continuing in order to evaluate secondary endpoints including OS.
Source: Company Press Release