Eli Lilly announced that its Phase 3 RANGE study of Cyramza (ramucirumab) met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement. The Phase 3 global, randomized, double-blinded, placebo-controlled trial is evaluating ramucirumab in combination with docetaxel in patients with locally advanced or unresectable or metastatic urothelial carcinoma whose disease progressed on or after platinum-based chemotherapy. Bladder cancer accounts for the majority of all urothelial carcinoma.
With these results, RANGE is the first Phase 3 study of any therapy to show superior PFS over chemotherapy in a post-platinum setting in urothelial cancer. Also, ramucirumab is the first antiangiogenic agent to extend PFS in a Phase 3 trial in urothelial cancer. Patients previously treated with a checkpoint inhibitor were allowed to enroll in the RANGE study.
The safety profile observed in the RANGE study at this analysis was consistent with what has been previously observed for ramucirumab. Grade ≥3 adverse events occurring at a rate of five percent or greater and that were higher on the ramucirumab-plus-docetaxel arm compared to the placebo-plus-docetaxel arm were neutropenia, febrile neutropenia and hypertension.
"People with advanced urothelial cancer – an aggressive disease – who have progressed on prior therapy need more treatment options that can help to control their disease," Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology said.
Although the primary endpoint has been met, Lilly anticipates that overall survival (OS) results are likely to be required for global regulatory submissions. Final OS results are currently expected in mid-2018. Investigators, patients and Lilly study personnel involved in patient-level decision making will remain blinded to patient-treatment assignments until that time.
RANGE is the first Phase 3 trial investigating ramucirumab in urothelial cancer patients. In a Phase 2 study in the same treatment setting, patients treated with ramucirumab and docetaxel showed a statistically significant improvement in PFS and disease control rate, and a numerically higher objective response rate, compared to the docetaxel-only arm. Overall, RANGE is the sixth positive Phase 3 trial of ramucirumab to date. Previously completed Phase 3 studies of ramucirumab have demonstrated benefit in advanced forms of gastric, non-small cell lung and colorectal cancer – three of the world's leading causes of cancer-related death.