The phase 3 KEYNOTE-045 trial investigating the use of pembrolizumab (Keytruda, Merck), an anti-programmed death-1 (PD-1) therapy, in patients with previously treated advanced urothelial cancer has met its primary endpoint of overall survival. In the study, pembrolizumab was superior compared with the investigator’s choice of chemotherapy. Based on a prespecified interim analysis, an independent data monitoring committee recommended that the trial be stopped early.
KEYNOTE-045 was a pivotal, randomized study evaluating pembrolizumab monotherapy compared with investigator-choice chemotherapy (paclitaxel, docetaxel, or vinflunine) in patients with metastatic or locally advanced or unresectable (inoperable) urothelial cancer that has recurred or progressed after platinum-based chemotherapy. The coprimary endpoints were overall survival and progression-free survival. Secondary endpoints included the overall response rate, the duration of response, and safety. A total of 542 subjects were randomly assigned to receive pembrolizumab (200 mg every three weeks) or the investigator’s choice of paclitaxel (175 mg/m2 every three weeks), docetaxel (75 mg/m2 every three weeks), or vinflunine (320 mg/m2 every three weeks).
Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab 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.
Pembrolizumab is administered as an intravenous infusion over 30 minutes for the following indications:
According to Merck, the pembrolizumab clinical development program includes more than 30 tumor types in more than 360 clinical trials, including nearly 200 trials that combine pembrolizumab with other cancer treatments. For genitourinary cancers, Merck has 27 trials under way involving pembrolizumab as monotherapy and in combination, including four registration-enabling studies.
Source: Merck; October 21, 2016.