Eli Lilly has announced that a Phase II study of its Cyramza (ramucirumab) in combination with docetaxel met its primary endpoint, demonstrating a statistically significant increase in progression-free survival (PFS) for patients with locally advanced or metastatic urothelial carcinoma who failed prior platinum-based therapy.
Final results of the Phase II trial were presented at the European Cancer Congress (ECC2015) in Vienna, Austria (Abstract #2508) on September 27. Based on these findings, Lilly said that recently it had initiated a Phase III trial called Range, which has begun to enroll patients.
“We are encouraged with these promising findings that could help lead to much-needed progress in this area – people with advanced urothelial carcinoma have limited treatment options today,” said Daniel Petrylak, M.D., professor of medicine (medical oncology) and of urology at Yale University Cancer Center and the study’s principal investigator. “This is an aggressive type of cancer and unfortunately, despite available first-line therapies, most patients who have disease progression eventually succumb to their disease. Currently, there are no agents specifically approved in the U.S., nor is there a consistently-employed single standard of care in the U.S. or globally, for the treatment of second-line bladder cancer.”
The company says that the three-arm trial evaluated 140 patients with advanced carcinoma of the urothelial tract (bladder, urethra, ureter, or renal pelvis) who, after a first-line platinum-based chemotherapy regimen, had relapsed up to one year following the initial treatment. Patients were randomized to receive either a combination of ramucirumab and docetaxel (n=46), docetaxel alone (n=45), or a combination of icrucumab and docetaxel (n=49). Treatment continued until disease progression or toxicity levels resulted in an interruption of treatment with one or more of the study medicines.
Furthermore, Median PFS, the study’s primary endpoint, was 5.4 months (HR 0.389; 95% CI: 0.389 0.235-0.643; p < 0.001) on the ramucirumab-docetaxel arm as compared to 2.8 months for patients treated with docetaxel alone, and 1.6 months for those treated with icrucumab and docetaxel. Objective response rate (ORR) results – or patients who achieved either a complete response or partial response to treatment – also favored the ramucirumab combination arm with a significantly higher confirmed ORR (24%) compared to those on the docetaxel arm (9%) and the icrucumab combination arm (12%). A statistically significant benefit in disease control rate – or patients who achieved complete response, partial response, or stable disease – was identified on the ramucirumab arm (78%) versus the docetaxel arm (58%) and the icrucumab arm (45%). While the study was not powered for overall survival (OS), results favored the ramucirumab combination arm, but were not statistically significant, with 10.4 months median OS identified on the ramucirumab arm compared to 9.2 months on the docetaxel arm and 6.7 months on the icrucumab arm.
The observed safety findings are consistent with prior Phase III studies of ramucirumab and docetaxel. The most common ( > 5% incidence) grade ≥3 adverse events occurring at a higher rate on the ramucirumab-plus-docetaxel arm compared to the docetaxel arm were fatigue (35% vs. 13%), febrile neutropenia (17% vs. 13%), pneumonia (13% vs. 9%), anemia (13% vs. 7%), sepsis (11% vs. 7%), edema (9% vs. 2%), diarrhea (7% vs. 2%), intestinal obstruction (7% vs. 2%), urinary tract infection (7% vs. 2%), hypertension (7% vs. 0%), stomatitis (7% vs. 0%), and thrombocytopenia (7% vs. 0%).
The Phase III RANGE study, which is currently enrolling patients, is a randomized, double-blind, placebo-controlled study of ramucirumab and docetaxel versus placebo and docetaxel in patients with locally advanced or unresectable metastatic urothelial carcinoma whose disease progressed on or after platinum-based chemotherapy (ClinicalTrials.gov Identifier: NCT02426125).
“We are pleased to advance this CYRAMZA regimen into Phase III clinical development and look forward to that trial’s results,” said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. “Our excitement with the overall clinical development of CYRAMZA continues to grow, with the RANGE trial in bladder cancer marking another tumor type in late-stage evaluation in this broad development program.”