- KEYNOTE-564 is the first Phase 3 trial to demonstrate superior overall survival (OS) with adjuvant therapy compared to placebo in patients with RCC
- Late-breaking OS results selected for the official Press Program at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium
Reno, Nevada (UroToday.com) -- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 3 KEYNOTE-564 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. These late-breaking data are being presented during an oral session for the first time today at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium (abstract #LBA359) and are included in the official ASCO GU Press Program.
At the third pre-specified interim analysis (median follow-up of 57.2 months [range, 47.9−74.5 months]), KEYTRUDA as adjuvant therapy significantly improved overall survival (OS), the trial’s key secondary endpoint, by 38% (HR=0.62 [95% CI, 0.44−0.87]; p=0.002) compared to placebo. At 48 months, the estimated OS rate was 91.2% for patients who received KEYTRUDA compared to 86.0% for patients who received placebo. The OS benefit for patients who received KEYTRUDA was observed across key subgroups.
“For patients with renal cell carcinoma, up to 40% may experience recurrence following surgery, at which point there is a significantly lower chance of survival,” said Dr. Toni K. Choueiri, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine, Harvard Medical School. “Results from KEYNOTE-564 show that pembrolizumab as adjuvant therapy significantly improved overall survival by 38% compared to placebo, becoming the first ever Phase 3 adjuvant trial to show improved survival for renal cancer patients at risk of recurrence after surgery.”“The positive overall survival results from KEYNOTE-564 build upon the disease-free survival data, which supported approvals of KEYTRUDA for this indication worldwide,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “This is the second KEYTRUDA study to demonstrate a significant overall survival benefit in an earlier stage of cancer, and these new results add to the progress we’re making in earlier stages of disease.”
As previously reported, at an earlier pre-specified interim analysis with a median follow-up of 24.1 months, KEYNOTE-564 met its primary endpoint of disease-free survival (DFS), reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; one-sided p=0.001) compared to placebo. At this third interim analysis, the DFS benefit was consistent with these previously reported data, with KEYTRUDA as adjuvant therapy reducing the risk of disease recurrence or death by 28% (HR=0.72 [95% CI, 0.59-0.87]) compared to placebo.
KEYTRUDA is approved for the adjuvant treatment of patients with RCC in the U.S., European Union, Japan and other countries worldwide based on DFS data from KEYNOTE-564, which were first presented at the 2021 ASCO Annual Meeting. Merck is currently working with health authorities to include these OS data in the full KEYTRUDA prescribing information.
Merck has a broad clinical development program in RCC across multiple settings, including adjuvant and advanced disease, utilizing KEYTRUDA as monotherapy or in combination with WELIREG (belzutifan, Merck’s oral hypoxia-inducible factor-2 alpha [HIF-2α] inhibitor), LENVIMA (lenvatinib, a multi-targeted VEGF TKI, in collaboration with Eisai) and quavonlimab (a CTLA-4 monoclonal antibody being developed under an agreement with Akeso Inc.).
Study design and additional data from KEYNOTE-564
KEYNOTE-564 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03142334) evaluating KEYTRUDA for the adjuvant treatment of patients with RCC who have undergone nephrectomy and who have disease that is intermediate-high risk, high risk or M1 no evidence of disease (NED). The primary endpoint is DFS as assessed by investigator review, and secondary endpoints include OS and safety. The study enrolled 994 patients who were randomized 1:1 to receive either KEYTRUDA (200 mg intravenously [IV] on Day 1 of each three-week cycle for up to 17 cycles) or placebo (saline solution IV on Day 1 of each three-week cycle for up to 17 cycles).
The OS benefit for patients who received KEYTRUDA was observed across key subgroups, including in patients with M0 disease (HR=0.63 [95% CI, 0.44-0.90]), M1 NED (HR=0.51 [95% CI, 0.15-1.75]), PD-L1 Combined Positive Score (CPS) <1 (HR=0.65 [95% CI, 0.31−1.38]) or CPS ≥1 (HR=0.62 [95% CI, 0.42−0.91]), and in patients with presence (HR=0.69 [95% CI, 0.28−1.70]) or absence (HR=0.57 [95% CI 0.39−0.84]) of sarcomatoid features.
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were observed. Treatment-related adverse events (TRAEs) occurred in 79.1% of patients (n=386) in the KEYTRUDA arm and 53.0% of patients (n=263) in the placebo arm. Grade 3-4 TRAEs occurred in 18.6% of patients in the KEYTRUDA arm and 1.2% of patients in the placebo arm. Treatment-related adverse events resulting in discontinuation of any treatment occurred in 18.2% of patients in the KEYTRUDA arm and 0.8% of patients in the placebo arm. No treatment-related deaths occurred.
Source: Merck. (2024). Merck’s KEYTRUDA® (pembrolizumab) Reduced the Risk of Death by 38% Versus Placebo as Adjuvant Therapy for Patients With Renal Cell Carcinoma (RCC) at an Increased Risk of Recurrence Following Nephrectomy [Press release]. https://www.merck.com/news/mercks-keytruda-pembrolizumab-reduced-the-risk-of-death-by-38-versus-placebo-as-adjuvant-therapy-for-patients-with-renal-cell-carcinoma-rcc-at-an-increased-risk-of-recurrence-follow/.
Related Content: ASCO GU 2024: Overall Survival Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab vs Placebo for the Treatment of Clear Cell RCC