Merck’s KEYTRUDA® Significantly Improved Disease-Free Survival as Adjuvant Therapy Versus Observation in High-Risk Patients With Localized Muscle-Invasive and Locally Advanced Urothelial Carcinoma After Surgery

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 3 AMBASSADOR (A031501)/KEYNOTE-123 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, for the adjuvant treatment of high-risk patients with localized muscle-invasive urothelial carcinoma (MIUC) and locally advanced resectable urothelial carcinoma. These late-breaking data are being presented for the first time today during an oral abstract session at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium (abstract #LBA531).

At the trial’s first pre-specified interim analysis, after a median follow-up of 22.3 months, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in one of the study’s dual primary endpoints of disease-free survival (DFS), reducing the risk of disease recurrence or death by 31% (HR=0.69 [95% CI, 0.54-0.87]; p=0.001) versus observation in these patients after surgery. Median DFS was 29.0 months (95% CI, 21.8-not evaluable [NE]) for KEYTRUDA and 14.0 months (95% CI, 9.7-20.20) for observation, an improvement of 15 months. These DFS results were consistent regardless of patients’ PD-L1 expression status. The trial’s other dual primary endpoint of overall survival (OS) did not reach statistical significance at the time of this interim analysis and will continue to be followed as data mature (HR=0.98 [95% CI, 0.76-1.26]; p=0.88). After a median follow-up of 36.9 months, median OS was 50.9 months (95% CI, 43.8-NE) for KEYTRUDA versus 55.8 months (95% CI, 53.3-NE) for observation.

“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,” said Dr. Andrea Apolo, principal investigator and chief of the Bladder Cancer Section, Genitourinary Malignancies Branch, National Cancer Institute (NCI), part of the National Institutes of Health. “In this trial, adjuvant pembrolizumab [KEYTRUDA] reduced the risk of disease recurrence or death from any cause by 31% versus observation, demonstrating the potential of using pembrolizumab [KEYTRUDA] 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.”

“These Phase 3 data mark the first time KEYTRUDA has shown a clinically meaningful improvement in DFS as adjuvant therapy in urothelial carcinoma,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “Results from this pivotal study support KEYTRUDA as a potential new adjuvant option for these patients and demonstrate the expanding role of KEYTRUDA into earlier stages of resectable muscle-invasive bladder cancer.”

Merck has an extensive clinical development program evaluating KEYTRUDA as monotherapy and in combination with other anti-cancer therapies across all stages of bladder cancer, including non-muscle-invasive, muscle-invasive and metastatic. Phase 3 studies in muscle-invasive bladder cancer include the KEYNOTE-866 trial, as well as the Phase 3 KEYNOTE-B15 and Phase 3 KEYNOTE-905 trials, which are being conducted in collaboration with Pfizer (formerly Seagen) and Astellas.

Study design and additional data from AMBASSADOR/KEYNOTE-123

AMBASSADOR (A031501)/KEYNOTE-123 is a randomized, open-label Phase 3 trial (, NCT03244384) evaluating KEYTRUDA versus observation for the adjuvant treatment of patients with localized MIUC and locally advanced resectable urothelial carcinoma. The dual primary endpoints are OS and DFS, and secondary endpoints include OS and DFS in PD-L1 positive and negative patients and safety. The trial enrolled 702 patients who were randomized to receive KEYTRUDA (200 mg intravenously every three weeks for up to 18 cycles) or undergo observation.

17.4% of patients receiving KEYTRUDA withdrew from the trial without event versus 27.2% from the observation arm. Seventy-six patients (22%) in the observation arm received an immune checkpoint inhibitor following a DFS event.

The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Grade ≥3 adverse events occurred in 48.4% of patients receiving KEYTRUDA versus 31.8% of patients under observation.

This trial was sponsored by the U.S. NCI, part of the National Institutes of Health. Alliance for Clinical Trials in Oncology designed and led the trial with funding from the NCI and participation from all the National Clinical Trials Network Groups. Merck provided funding and support through a Cooperative Research and Development Agreement between Merck and NCI.

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