Merck has announced results from the phase 3 AMBASSADOR (KEYNOTE-123) trial, demonstrating that use of pembrolizumab (Keytruda) resulted in statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the adjuvant treatment of high-risk patients with localized muscle-invasive urothelial carcinoma or locally advanced resectable urothelial carcinoma, according to a press release. The results were presented as late-breaking oral abstract at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.
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“These phase 3 data mark the first time [pembrolizumab] has shown a clinically meaningful improvement in DFS as adjuvant therapy in urothelial carcinoma,” Marjorie Green, MD, senior vice president and head of oncology in global clinical development at Merck Research Laboratories, said in the press release. “Results from this pivotal study support [pembrolizumab] as a potential new adjuvant option for these patients and demonstrate the expanding role of [pembrolizumab] into earlier stages of resectable muscle-invasive bladder cancer.”
About the AMBASSADOR Trial
Title: Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer
ClinicalTrials.gov ID: NCT03244384
Sponsor: National Cancer Institute
Estimated Completion Date: June 2025
The trial was a randomized, open-label phase 3 trial to evaluate pembrolizumab compared to observation in the adjuvant treatment of patients with localized muscle-invasive urothelial carcinoma and locally advanced resectable urothelial carcinoma. The trial included 702 individuals who randomly received pembrolizumab 200 mg intravenously every 3 weeks for 18 cycles or underwent observation alone. Approximately 17.4% who received pembrolizumab withdrew from the trial without an event compared to 27.2% from the observation arm, according to the press release.
After a median 22.3 months of follow-up, pembrolizumab reduced the risk of disease recurrence or death by 31% compared to observation post-surgery in the patient population, according to the press release. The median DFS was 29 months for pembrolizumab compared to 14 months for observation only. The results were consistent for patients regardless of their PD-L1 expression status.
At the time of the interim analysis, the dual primary endpoint of overall survival (OS) did not reach statistical significance. According to the press release, the data will continue to be followed until mature. As of the 36.9-month follow-up, the median OS was 50.9 months compared to 55.8 for observation post-surgery.
“Even after undergoing radical surgery with the goal of removing all cancerous tumors, up to half of patients with muscle-invasive bladder cancer still experience high rates of cancer recurrence,” Andrea Apolo, MD, principal investigator and chief of the Bladder Cancer Section of the Genitourinary Malignancies Branch at the National Cancer Institute, part of the National Institutes of Health, said in the press release. “In this trial, adjuvant pembrolizumab reduced the risk of disease recurrence or death from any cause by 31% versus observation, demonstrating the potential of using pembrolizumab after surgery for high-risk patients with persistent muscle-invasive or locally advanced urothelial carcinoma who have high tumor stage, lymph node involvement, or positive margins at surgery to help prevent their cancer from returning.”
The safety profile in this trial was consistent with that observed in previous studies, and no new safety signals were identified. Grade 3 or higher adverse events occurred in 48.4% of individuals receiving pembrolizumab compared to 31.8% who underwent observation alone.
Phase 3 studies for muscle-invasive bladder cancer also include KEYNOTE-866, KEYNOTE-B15, and KEYNOTE-905, conducted in collaboration with Pfizer and Astellas.
Merck’s Keytruda (pembrolizumab) significantly improved disease-free survival (DFS) as adjuvant therapy versus observation in high-risk patients with localized muscle-invasive and locally advanced urothelial carcinoma after surgery. News release. Merck. January 26, 2024. Accessed January 26, 2024. https://www.merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-disease-free-survival-dfs-as-adjuvant-therapy-versus-observation-in-high-risk-patients-with-localized-muscle-invasive-and-locall/