Lilly Announces Phase 3 RANGE Urothelial Cancer Trial of CYRAMZA® (ramucirumab) Met Primary Endpoint, Improving Progression-Free Survival

Randomized, placebo-controlled study confirms ramucirumab, in combination with docetaxel, significantly extended progression-free survival (PFS) in previously treated patients with locally advanced or unresectable or metastatic urothelial carcinoma

INDIANAPOLIS, May 31, 2017 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today 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. Detailed efficacy and safety results will be submitted for presentation at a future medical meeting.

"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," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology.

While there have been several recent advancements to treat this type of cancer, most patients progress despite treatment with existing therapies, including immune checkpoint inhibitors. Dr. Garraway added, "Until now, no Phase 3 study has demonstrated superior PFS over chemotherapy in this setting. These results are encouraging and we look forward to seeing the overall survival results when they are mature. Lilly would like to thank the patients, investigators and clinical trial sites that are participating in this study."

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.1 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.

Notes to Editor

About the RANGE Study
The RANGE trial, which enrolled 531 patients globally, is a randomized, double-blinded study designed to evaluate the safety and efficacy of ramucirumab and docetaxel versus placebo and docetaxel in patients with locally advanced or unresectable or metastatic urothelial carcinoma whose disease progressed on or after platinum-based chemotherapy. The trial includes: 1) patients who progressed following adjuvant and/or neoadjuvant therapy; 2) patients who progressed following first-line metastatic therapy; and 3) patients who had received prior platinum-based and immune checkpoint inhibitor regimens. The trial's primary endpoint is progression-free survival and other secondary endpoints include overall survival, objective response rate, disease control rate and duration of response.

About Urothelial Cancer 
Urothelial cancer includes carcinomas 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 accounts for the majority of all urothelial carcinoma.

Worldwide, bladder cancer ranks ninth in the top most common cancers overall,2 and the ninth leading cause of cancer-related deaths, afflicting approximately 430,000 people per year and resulting in more than 165,000 deaths.3 The global incidence of bladder cancer increased 11 percent from 2008 to 2012.  In the U.S., bladder cancer is the sixth most common and deadly cancer,4 with an estimated 79,000 new cases and nearly 17,000 deaths expected in 2017.5

Generally, this is an aggressive disease and unfortunately, despite recently approved therapies, most patients who have disease progression will eventually succumb to their cancer.

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.

Ramucirumab is being investigated in a broad global development program that has enrolled more than 10,000 patients across more than 70 trials worldwide. There are several studies underway or planned to investigate ramucirumab as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types.

Ramucirumab 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. Ramucirumab 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

 


WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, AND
IMPAIRED WOUND HEALING

 

Hemorrhage: CYRAMZA increased the risk of hemorrhage and gastrointestinal hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding.

 

Gastrointestinal Perforation: CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.

 

Impaired Wound Healing: Impaired wound healing can occur with antibodies inhibiting the VEGF pathway. Discontinue CYRAMZA therapy in patients with impaired wound healing. Withhold CYRAMZA prior to surgery and discontinue CYRAMZA if a patient develops wound healing complications.

 

Warnings and Precautions

Hemorrhage

Arterial Thromboembolic Events (ATEs)

Hypertension

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 Warning for hemorrhage, gastrointestinal perforation, and impaired wound healing.
RB-P-HCP ISI 16FEB2017

About Lilly Oncology 
For more than 50 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. P-LLY    

© Lilly USA, LLC 2017. ALL RIGHTS RESERVED.

CYRAMZA is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.

Lilly Forward-Looking Statement
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about ramucirumab as a potential treatment for patients with locally advanced or unresectable or metastatic urothelial carcinoma, and reflects Lilly's current beliefs. 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 ramucirumab will achieve its primary study endpoints, receive additional regulatory approvals or be commercially successful. 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.

 

1 Petrylak DP, Tagawa ST, Kohli M,, etal. Docetaxel As Monotherapy or Combined With Ramucirumab or Icrucumab in Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: An Open-Label, Three-Arm, Randomized Controlled Phase II Trial. J Clin Oncol. 2016;34(13):1500-9.

2 World Cancer Research Fund International. "Bladder Cancer Statistics" http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/bladder-cancer-statistics (Accessed May 30, 2017)

3 World Health Organization. "GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide 2012.  http://globocan.iarc.fr/Pages/fact_sheets_population.aspx (Accessed May 30, 2017)

4 National Institute of Health National Cancer Institute Surveillance, Epidemiology, and End Results Program. "Cancer Stat Facts: Bladder Cancer" https://seer.cancer.gov/statfacts/html/urinb.html (Accessed May 30, 2017).

5 American Cancer Society. "What are the key statistics about bladder cancer?" http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics. (Accessed May 30, 2017).

 

Refer to:  
Tracy Henrikson; tracy.henrikson@lilly.com; 609-240-3902 (media) 
Phil Johnson; johnson_philip_l@lilly.com; 317-655-6874 (investors)       

 

Eli Lilly and Company logo. (PRNewsFoto, Eli Lilly and Company)

 

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