Merck’s Keytruda Poised for Bladder Cancer Expansion with New Phase III Data

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Pictured: Merck signage outside its office in California/iStock, hapabapa

Merck on Thursday reported that its blockbuster PD-1 inhibitor Keytruda (pembrolizumab) met one of its dual primary endpoints in the Phase III AMBASSADOR trial in muscle-invasive urothelial carcinoma.

Details of the study were limited but Merck said that at a pre-specified interim analysis review Keytruda treatment led to a statistically significant and clinically meaningful improvement in disease-free survival compared with simple observation. AMBASSADOR is ongoing and will continue to assess the effects of Keytruda on overall survival (OS), the study’s second primary endpoint.

The promising initial data from AMBASSADOR point to the “potential of Keytruda to prevent recurrence” in patients who had undergone surgery, Marjorie Green, senior vice president and head of late-stage oncology, global clinical development at Merck Research Laboratories, said in a statement.

AMBASSADOR, also known as KEYNOTE-123, is a randomized and open-label study enrolling approximately 740 patients with localized muscle-invasive or locally advanced urothelial carcinoma. Pembrolizumab was administered intravenously for up to 18 cycles, while comparators in the observation arm were given no intervention beyond routine clinical procedures including a CT scan, blood analysis and an MRI.

Aside from efficacy, the study also evaluated Keytruda’s safety profile in this indication and found no new signals of concern. Keytruda’s adverse event profile in AMBASSADOR was consistent with what had been established in prior trials.

Merck will present the study’s results at an upcoming medical meeting and discuss the data with regulators.

Keytruda, a PD-1-blocking antibody, was first approved in bladder cancer in May 2017, allowing its use in specific cases of locally advanced or metastatic urothelial carcinoma. The blockbuster cancer therapy has since picked up more approvals in this disease area, including one for non-muscle invasive bladder cancer. Keytruda has not yet been authorized to treat muscle-invasive urothelial carcinoma.

Thursday’s Phase III victory continues Keytruda’s winning streak in bladder cancer. In September 2023, Merck reported that the PD-1 blocker aced a collaborative late-stage study with Astellas and Seagen in locally advanced and metastatic urothelial cancer. Patients treated with the combination of Keytruda and Padcev (enfortumab vedotin-ejfv) saw significant improvements in OS and progression-free survival (PFS), the study’s dual primary endpoints, compared with chemotherapy.

However, Merck’s blockbuster asset has not been without its recent setbacks. Late last month, Keytruda stumbled in two Phase III studies in non-small cell lung cancer when given with Eisai’s Lenvima (lenvatinib). In this indication, the combination regimen failed to significantly boost PFS and OS when given as either a first-line or second-line intervention.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

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