Abemaciclib - Lilly's Oral CDK 4/6 Inhibitor - Shows Single-Agent Activity In A Phase I Study For Patients With A Specific Type Of Lung Cancer

This early phase study also evaluated an abemaciclib combination in hormone receptor positive metastatic breast cancer patients

INDIANAPOLIS, May 14, 2014 /PRNewswire/ -- Abemaciclib, an oral drug administered twice daily, currently in development by Eli Lilly and Company (NYSE: LLY), has shown evidence of single-agent activity in patients with advanced non-small cell lung cancer in a Phase I study released ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting to be held in Chicago, Ill. Also released was data from another cohort of this study which evaluated the safety of the combination of abemaciclib plus fulvestrant in women with hormone receptor positive metastatic breast cancer.

Cyclin-dependent kinases play a key role in regulating cell cycle progression. In many cancers, there is a loss of control in regulating the cell cycle in response to increased signaling from CDK 4/6. As a result, there is uncontrolled growth of cancer cells. Lilly's abemaciclib (LY2835219) is a cell-cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting CDK 4 and 6.

"These data add to the growing body of evidence to support our Phase III development of abemaciclib," said Richard Gaynor, M.D., senior vice president of product development and medical affairs for Lilly Oncology. "We currently have a Phase III program for breast cancer and plan to advance into Phase III for lung cancer yet this year."

A Phase I trial was conducted with expansion cohorts to evaluate the safety, pharmacokinetics (or how a body interacts with a drug) and antitumor activity of abemaciclib in five different tumor types, which include glioblastoma, melanoma, colorectal cancer, non-small cell lung cancer (NSCLC) and metastatic breast cancer.

Abemaciclib in NSCLC (Abstract #8026)
KRAS genes, when mutated, are known to turn normal cells into cancerous cells. And existing studies suggest that the presence of KRAS mutation in NSCLC patients is indicative of a poor prognosis, which makes this an important area of research.[1] In preclinical research, there was evidence for greater sensitivity to abemaciclib in reducing the growth of cancer cells when used in NSCLC models with KRAS mutations. In the Phase I study, 57 patients with advanced NSCLC who progressed or relapsed after standard treatments were enrolled. The patients enrolled received a median of four prior regimens, 29 patients had KRAS mutations while 24 were KRAS wild-type, and KRAS status was unknown for 4 patients. Patients received abemaciclib twice daily during the study.

Disease control rate – defined as patients demonstrating either a complete response, partial response or stable disease – was 49 percent for patients on abemaciclib, including two partial responses and 26 patients with stable disease. Consistent with preclinical data, the disease control rate was higher for patients with KRAS mutant type (55%) versus those with KRAS wild-type (38%).

The most common grade 3 adverse events (greater than 5% incidence) were leukopenia (14%) and neutropenia (9%). No patients in the lung cancer cohort experienced grade 4 adverse events. Less than two percent of patients discontinued due to adverse events in this study cohort.

"KRAS mutations are common in patients with NSCLC, but there have been few clinical advances in our treatment for these patients," said Jonathan W. Goldman, M.D. of UCLA's Jonsson Comprehensive Cancer Center, investigator of the trial's lung cancer cohort and study presenter. "The results of the lung cohort of this study – which showed that abemaciclib could decrease tumor size in this patient population – suggest further clinical investigation of abemaciclib as a single agent for the treatment of NSCLC is warranted, with a particular focus on those tumors with KRAS mutations."

Abemaciclib in Metastatic Breast Cancer (Abstract #534)
In this cohort of the Phase I study, 18 patients with hormone receptor positive metastatic breast cancer were treated with abemaciclib twice daily. Patients also received the anti-estrogen treatment fulvestrant once per month. The 18 patients had received a median of four prior systemic regimens.

The primary goal of this cohort of the study was to examine the safety profile of the combination treatment. The most common grade 3 adverse events (greater than 5% incidence) were neutropenia (33%), leukopenia (22%), abdominal pain (11%), diarrhea (6%) and fatigue (6%). No grade 4 toxicities were reported and no patients discontinued due to adverse events.

"We have seen patients with hormone receptor positive metastatic breast cancer whose tumors respond to treatment with abemaciclib alone even after their disease stopped responding to other treatments. The results of this study cohort evaluating the combination of abemaciclib and fulvestrant are encouraging and support further development," said Amita Patnaik, M.D., associate director of clinical research at South Texas Accelerated Research Therapeutics, principal investigator of the trial's breast cancer cohort.

A Phase III study is planned to evaluate the safety and efficacy of abemaciclib and fulvestrant combination.

About Lung Cancer
Lung cancer is the leading cause of cancer death in the U.S. and most other countries, killing nearly 1.6 million people worldwide each year.[2] In the U.S., lung cancer is responsible for nearly 30 percent of all cancer deaths, more than those from breast, colon and prostate cancers combined.[3] Advanced (stage IV) NSCLC is a very difficult-to-treat cancer and the prognosis for patients with NSCLC is poor when locally advanced or metastatic.[4] NSCLC is much more common than other types of lung cancer, and accounts for 85 percent of all lung cancer cases.

About Metastatic Breast Cancer
Breast cancer is the most common cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.[5] In the United States each year, more than 232,000 new cases of invasive breast cancer will be diagnosed and 40,000 women will die from breast cancer.[6] Of all diagnosed breast cancer cases in the U.S., 20 to 30 percent will become metastatic, spreading to other parts of the body with an estimated six to 10 percent of all new breast cancer cases initially stage IV, or metastatic.[7] Metastatic breast cancer is considered incurable, although those diagnosed can live with it as a chronic condition for many years.[8]

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 http://newsroom.lilly.com/social-channels.


Fulvestrant (Faslodex®), MedImmune/AstraZeneca

This press release contains forward-looking statements about the potential of abemaciclib (LY2835219) as treatment for various cancers 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. There is no guarantee that these products will be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

[1] Riely, Marks, and Pao. KRAS Mutations in Non–Small Cell Lung Cancer. Proc Am Thorac Soc Vol 6. pp 201–205, 2009.
[2] International Agency for Research on Cancer. GLOBOCAN 2012. Lung Cancer Estimated Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr. Accessed February 18, 2014.  
[3] American Cancer Society, Cancer Facts & Figures 2012, http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-031941.pdf. Accessed February 18, 2014.  
[4] National Cancer Institute. General information about non-small cell lung cancer. May 30, 2013. http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/healthprofessional/page1. Accessed February 18, 2014.  
[5]World Cancer Research Fund International, "Breast Cancer" http://www.wcrf.org/cancer_statistics/data_specific_cancers/breast_cancer_statistics.php . Accessed: February 7, 2014.
[6] American Cancer Society, "What are the key statistics about breast cancer?," http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics, Accessed: February 7, 2014
[7] Metastatic Breast Cancer Network, "Most Common Statistics Cited for MBC," http://mbcn.org/education/category/most-commonly-used-statistics-for-mbc, Accessed: February 7, 2014
[8] Metastatic Breast Cancer Network, "Most Common Statistics Cited for MBC," http://mbcn.org/education/category/most-commonly-used-statistics-for-mbc, Accessed: February 7, 2014

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