Merck has reported a significant breakthrough in its Phase III AMBASSADOR trial involving the blockbuster PD-1 inhibitor, Keytruda (pembrolizumab), for the treatment of muscle-invasive urothelial carcinoma.
While specific study details were limited, Merck revealed that Keytruda met one of its dual primary endpoints by demonstrating a statistically significant and clinically meaningful improvement in disease-free survival compared to observation alone during a pre-specified interim analysis.
The AMBASSADOR trial, also known as KEYNOTE-123, remains ongoing, with its second primary endpoint being the assessment of Keytruda’s impact on overall survival (OS). This early success in the study hints at Keytruda’s potential to prevent recurrence in patients who have undergone surgery, according to Marjorie Green, Senior Vice President and Head of Late-Stage Oncology at Merck Research Laboratories.
AMBASSADOR, a randomized and open-label study, enrolled approximately 740 patients with localized muscle-invasive or locally advanced urothelial carcinoma. Patients receiving Keytruda were administered the drug intravenously for up to 18 cycles, while those in the observation arm received no intervention beyond routine clinical procedures, including imaging and blood analysis.
In addition to evaluating efficacy, the study also assessed the safety profile of Keytruda in this indication and found no new signals of concern. The adverse event profile of Keytruda in AMBASSADOR remained consistent with previous trial data.
Merck plans to present the full results of the study at an upcoming medical meeting and engage in discussions with regulatory authorities.
Keytruda, a PD-1-blocking antibody, was initially approved for bladder cancer in May 2017, specifically for certain cases of locally advanced or metastatic urothelial carcinoma. It has since gained additional approvals in this disease area, including non-muscle invasive bladder cancer. However, Keytruda had not yet been authorized for the treatment of muscle-invasive urothelial carcinoma.
This recent Phase III success in the AMBASSADOR trial adds to Keytruda’s impressive track record in bladder cancer. In September 2023, Merck reported positive results from a collaborative late-stage study with Astellas and Seagen, demonstrating significant improvements in overall survival and progression-free survival for patients treated with the combination of Keytruda and Padcev (enfortumab vedotin-ejfv) compared to chemotherapy in locally advanced and metastatic urothelial cancer.
Despite these victories, Keytruda faced setbacks in late-stage Phase III studies in non-small cell lung cancer when administered in combination with Eisai’s Lenvima (lenvatinib). In this context, the combination regimen failed to significantly improve progression-free survival and overall survival, whether used as a first-line or second-line intervention.