Lilly Reports Top-Line Results from CYRAMZA® (ramucirumab) Phase 3 Study in First-Line Advanced Gastric Cancer

INDIANAPOLIS, Dec. 8, 2017 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced top-line results from its Phase 3 RAINFALL study of CYRAMZA® (ramucirumab) in combination with cisplatin and capecitabine or 5-FU (5-fluorouracil) in the first-line treatment of patients with HER2-negative metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The trial met its primary endpoint of progression-free survival (PFS) but did not improve overall survival (OS), a secondary endpoint. The results will be submitted for presentation at a future medical meeting.

The safety profile observed in the RAINFALL study 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-cisplatin-and-capecitabine/5-FU arm compared to the placebo-plus-cisplatin-and-capecitabine/5-FU arm were hypertension, hand-foot syndrome, and fatigue.

"While we hoped that the positive PFS outcome would have translated into an OS benefit, these RAINFALL results highlight the challenges associated with improving outcomes for people with advanced gastric cancer," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "This is underscored by the fact that there have been no major advances over standard chemotherapy in the first-line HER2-negative gastric cancer treatment setting in the last decade."

Dr. Garraway added, "Lilly is deeply committed to patients with this aggressive disease, and CYRAMZA remains a standard of care in the second-line treatment paradigm for advanced gastric cancer patients around the world. We thank the patients, their caregivers and investigators for their support of and participation in the RAINFALL study."

The company does not intend to seek regulatory approval based on the results of the RAINFALL study. The outcome of RAINFALL does not have any impact on current ramucirumab approvals.

After becoming the first FDA-approved agent to treat advanced gastric cancer after prior chemotherapy in 2014 based on two pivotal Phase 3 studies, ramucirumab is now a standard of care in this setting around the world. This is supported by global and local treatment guidelines, including NCCN, JGCA and ESMO.

Overall, there have been six positive Phase 3 trials 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. An ongoing Phase 3 trial in advanced urothelial carcinoma has also met its primary endpoint of PFS; those initial data were presented at the ESMO 2017 Congress and OS data are expected in mid-2018. Two other ongoing Phase 3 studies of ramucirumab - in hepatocellular carcinoma and EGFR-positive non-small cell lung cancer - are ongoing, with expected data readouts in 2018.

Notes to Editors

About RAINFALL
RAINFALL is a global, randomized, double-blinded, placebo-controlled Phase 3 study of ramucirumab in combination with cisplatin and capecitabine as a first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Study participants unable to take capecitabine (tablets) were given 5-fluorouracil (5-FU).

Initiated in 2015, the study enrolled 645 patients across 19 countries in North America, Asia (Japan), Europe and Latin America. The primary endpoint of the RAINFALL trial is progression-free survival and key secondary endpoints include: overall survival; objective response rate; and safety. 

About Gastric Cancer 
Gastric cancer, also known as stomach cancer, is a major global health problem. Globally, it is the fifth most common cancer in the world, with one million new cases annually.1 Gastric cancer originates in the stomach. Cancer cells typically develop slowly and symptoms often do not appear until the disease is advanced and has already spread to other organs such as the liver, lungs and bones.2,3 Stomach cancer is the third leading cause of cancer deaths in the world, resulting in 723,000 deaths each year.1 The five-year survival rate for stomach cancer is 31 percent and five percent for advanced cases.4

Stomach cancer is much more common in the Far East than in the Western world.1 In the U.S., it is estimated that approximately 28,000 people will be diagnosed with stomach cancer and nearly 11,000 people will die from this type of cancer in 2017.5 In Japan, the incidence of stomach cancer is high. Of all cancers in Japan, stomach cancer is the second most common and it is the second-leading cause of cancer-related deaths, affecting approximately 108,000 people and killing approximately 52,000.

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.

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.

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 the RAINFALL trial and ramucirumab as a potential treatment for patients with gastric cancer 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 receive regulatory approvals or continue to 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 Globocan 2012 Cancer Fact Sheet. Stomach Cancer Estimated Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed November 29, 2017.

2 American Cancer Society. Signs and symptoms of stomach cancer. Updated February 10, 2016. http://www.cancer.org/cancer/stomachcancer/detailedguide/stomachcancer-signs-symptoms. Accessed November 29, 2017.

3 American Cancer Society. What is stomach cancer? Updated February 10, 2016. http://www.cancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-what-is-stomach-cancer. Accessed November 29, 2017.

4 American Cancer Society. Survival Rates for Stomach Cancer, by Stage. Available at: https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html. Accessed November 29, 2017.

5 American Cancer Society. What are the key statistics about stomach cancer? http://www.cancer.org/Cancer/StomachCancer/DetailedGuide/stomach-cancer-key-statistics. Updated May 27, 2014. Accessed November 29, 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)

 

View original content with multimedia:http://www.prnewswire.com/news-releases/lilly-reports-top-line-results-from-cyramza-ramucirumab-phase-3-study-in-first-line-advanced-gastric-cancer-300569229.html

SOURCE Eli Lilly and Company

News Provided by Acquire Media


Close window | Back to top