Merck’s KEYTRUDA® Significantly Improved Disease-Free Survival in Patients With Localized Muscle-Invasive and Locally Advanced Urothelial Carcinoma After Surgery

RAHWAY, N.J. — Merck & Co. (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 was 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 (ClinicalTrials.gov, 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.

 

About KEYTRUDA^® (pembrolizumab) injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

 

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.