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INDIANAPOLIS , Sept. 28, 2015 /PRNewswire/ -- A Phase II study of Eli Lilly and Company's (NYSE: LLY ) 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. Bladder cancer accounts for the vast majority of all urothelial carcinoma.
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 recently 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 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.
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."
About Urothelial Carcinoma and Bladder Cancer
Urothelial carcinoma are cancers that arise in the urothelial or transitional cells that line the urinary collecting system including the bladder, which is the most common site for this type of tumor. Other potential primary sites of this cancer include the renal pelvis, ureter, and urethra.
Bladder cancer is the sixth most common and deadly cancer in the U.S., i with an estimated 74,000 new cases and 16,000 deaths expected in 2015. ii Globally, bladder cancer ranks ninth in the top most common cancers overall, and the ninth leading cause of cancer-related death, affecting approximately 430,000 people per year and resulting in more than 165,000 deaths. i
About CYRAMZA ® (ramucirumab) In the U.S., CYRAMZA (ramucirumab) is approved for use as a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy. It is also approved in combination with docetaxel as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy. Additionally, it is approved with FOLFIRI as a treatment for people with metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
There are several additional studies underway or planned to investigate CYRAMZA as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types. This broad global development program has enrolled more than 7,000 patients across more than 50 trials of CYRAMZA worldwide.
CYRAMZA is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. CYRAMZA inhibited angiogenesis in an in vivo animal model.
About Angiogenesis and VEGF Protein Angiogenesis is the process of making new blood vessels. In a person with cancer, angiogenesis creates new blood vessels that give a tumor its own blood supply, allowing it to grow and spread.
Some tumors create proteins called VEGF. These proteins attach to the VEGF receptors of blood vessel cells causing new blood vessels to form around the tumors, enabling growth. Blocking the VEGF protein from linking to the blood vessels helps to inhibit tumor growth by slowing angiogenesis and the blood supply that feeds tumors. Of the three known VEGF receptors, VEGF Receptor 2 is linked most closely to VEGF-induced tumor angiogenesis.
INDICATIONS Gastric Cancer CYRAMZA, as a single agent or in combination with paclitaxel, is indicated for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Non-Small Cell Lung Cancer CYRAMZA, in combination with docetaxel, is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA.
Colorectal Cancer CYRAMZA, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
IMPORTANT SAFETY INFORMATION FOR CYRAMZA
Warnings and Precautions
Arterial Thromboembolic Events (ATEs)
Infusion-Related Reactions (IRRs)
Gastrointestinal Perforations
Impaired Wound Healing
Clinical Deterioration in Child-Pugh B or C Cirrhosis
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Proteinuria Including Nephrotic Syndrome
Thyroid Dysfunction
Embryofetal Toxicity
Most Common Adverse Reactions—Single Agent
Most Common Adverse Reactions—Combination With Paclitaxel
Most Common Adverse Reactions—Combination With Docetaxel
Most Common Adverse Reactions—Combination With FOLFIRI
Drug Interactions
Use in Specific Populations
Please see full Prescribing Information for CYRAMZA, including Boxed Warnings for hemorrhage, gastrointestinal perforation, and impaired wound healing.
RB-P HCP ISI 17SEP2015
About Lilly Oncology For more than fifty years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly's commitment to people with cancer, please visit www.LillyOncology.com .
About Eli Lilly and Company Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and newsroom.lilly.com/social-channels .
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about CYRAMZA (ramucirumab) as a potential treatment for patients with locally advanced or metastatic urothelial carcinoma and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that ramucirumab will achieve its primary study endpoints or receive regulatory approvals. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
i World Health Organization. "GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012" http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx . (Accessed September 25 , 2015).
ii American Cancer Society. "What are the key statistics about bladder cancer?" http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics . (Accessed September 25, 2015 ).
Refer To: Tracy Henrikson; [email protected] ; (609) 240-3902 (Lilly) Neil Hochman ; [email protected] ; (212) 453-2067 (TogoRun)
SOURCE Eli Lilly and Company