So the LEAP-011 trial is a first trial to evaluate the use of first-line pembrolizumab combined with lenvatinib in patients with advanced urothelial carcinoma who are ineligible to receive cisplatin-based chemotherapy or any platinum-based chemotherapy.
The rational came from the fact that pembrolizumab is an approved first-line therapy for cisplatin-ineligible patient, who have previously treated advanced urothelial carcinoma, and lenvatinib is an androgenic inhibitors, and has shown anti-tumoral activity in several advanced tumors...
So the LEAP-011 trial is a first trial to evaluate the use of first-line pembrolizumab combined with lenvatinib in patients with advanced urothelial carcinoma who are ineligible to receive cisplatin-based chemotherapy or any platinum-based chemotherapy.
The rational came from the fact that pembrolizumab is an approved first-line therapy for cisplatin-ineligible patient, who have previously treated advanced urothelial carcinoma, and lenvatinib is an androgenic inhibitors, and has shown anti-tumoral activity in several advanced tumors. And finally, we had results from Phase Ib/II study, the KEYNOTE-146 study, that showed that this combination had promising preliminary activity and manageable safety in these patient. So the trial enrolled patients, around 500 patients, but we had a data monitoring committee that regularly reviews the safety data, every three months. And the DMC determined the benefit to risk ratio of the combination, and based on the data, the DMC made the recommendation to stop enrollment. And so, finally, 487 patients were randomized in the trial. There was no difference in terms of PFS between the two groups, so pembrolizumab plus lenvatinib versus pembrolizumab plus placebo. There was no difference in terms of overall-survival. A small difference in terms of overall response rate, 33.1% in the pembrolizumab plus lenvatinib arm, versus 28.9% in the pembrolizumab plus placebo arm. And regarding the safety, I have to say that the safety was generally consistent with the known profile of pembrolizumab plus lenvatinib, and no new safety signals were detected, but again, the benefit to risk ratio for pembrolizumab plus lenvatinib was not considered positive so the study stopped enrollment based of the recommendation of the DMC.