The data presented were gathered from a multicenter Phase II study of enzastaurin as a second- or third-line treatment of NSCLC (ASCO Abstract #7543 ). The rationale for the study was based on en-zastaurin’s unique mechanism of action as a serine/threonine kinase inhibitor, which is believed to suppress signaling through the PKC-ß and PI3K/AKT pathways. Historically, over-expression and ac-tivity of PKC-ß and PI3K/AKT have been associated with poor prognosis and treatment resistance in NSCLC. The primary objective of the study was progression-free survival at six months. Secondary endpoints were safety and overall survival at 12 months.
“These data in NSCLC shed new light on the potential versatility of this agent,” said Richard Gaynor, M.D., vice president, cancer research and global oncology platform leader for Lilly. “Our objective with enzastaurin is to continue investigating the efficacy and safety of this unique molecule in order to determine the diseases where enzastaurin could have the most positive impact on patients.”
In the study, patients received 500 mg of oral enzastaurin, once daily, until disease progression or un-acceptable toxicity occurred. In the 54 patients enrolled, the median progression-free survival was 1.9 months (95% Confidence Interval: 1.7-1.9) and the progression-free survival rate at six months was 14% (95% CI: 4.4%-23.6%). The median overall survival was 9.9 months (95% CI: 6.5-14.6). The overall survival rate at 12 months was 46.3% (95% CI: 32.1%-60.5%). The most common toxicity was fatigue. Additional toxicities observed included ataxia (n=1), thromboembolism (n=1), anemia (n=1) and dizziness.
“Based on the encouraging survival and tolerability data gathered thus far, further evaluation of en-zastaurin in NSCLC, as a single agent or in combination, is warranted,” said chief investigator for the study, Gerold Bepler, M.D., Ph.D., chief of thoracic oncology at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida.
Additional data presented at ASCO this year examined studies of enzastaurin in breast cancer, first-line glioblastoma, ovarian and pancreatic cancers, as well as other solid tumors. Specifically, the data in-cluded: testing enzastaurin on cell signaling, proliferation and apoptosis in breast cancer, testing in Phase I/II with radiation combination therapy for first-line treatment of glioblastoma multiforme, a pre-clinical study on ovarian chemo-resistant cancer cell lines, testing for growth suppression in pancreatic cancer, as well as dosage testing on other solid tumors.
“Through a constant stream of innovation, we remain committed to fighting cancer,” said Gaynor. “By aggressively studying enzastaurin across multiple tumor types, we believe that we will find appropriate and innovative uses for this targeted therapy to help benefit patients.”
Enzastaurin is an oral, serine threonine kinase inhibitor which selectively targets the PKC-ß and PI3K/AKT signaling pathways. By blocking these key pathways frequently over-expressed in a wide variety of cancers, enzastaurin suppresses tumor cell proliferation, induces tumor cell death and inhibits tumor-induced angiogenesis. Enzastaurin is being evaluated in a Phase III trial (currently enrolling patients) as a maintenance therapy for the treatment of diffuse large B-cell lymphoma (DLBCL), as well as being evaluated in several Phase II studies across a variety of more common tumor types including: breast, colon, lung, ovarian and prostate cancers. More details on the enzastaurin Phase III trial, as well as information on global recruitment sites, may be found at www.clinicaltrials.gov, www.lillytrials.com or by calling 1-877-CTLilly (1-877-285-4559).
About Lilly Oncology, a Division of Eli Lilly and Company
For more than four decades, Lilly Oncology has been collaborating with cancer researchers to deliver innovative treatment choices and valuable programs to patients and their physicians. Inspired by courageous patients living with cancer, Lilly Oncology is providing treatments that are considered global standards of care and developing a broad portfolio of novel targeted therapies to accelerate the pace and progress of cancer care. To learn more about Lilly's commitment to cancer, please visit www.LillyOncology.com.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laborato-ries and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs.
This press release contains forward-looking statements about the potential of the investigational compound enzastaurin (LY317615) and reflects Lilly’s current beliefs. However, as with any pharmaceutical product under development, there are substantial risks and uncertainties in the process of development and regulatory review. There is no guarantee that the product will receive regulatory approvals, or that the regulatory approval will be for the indication(s) anticipated by the company. There is also no guarantee that the product will prove to 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.
Bepler, G, Oh Y, et al. A phase II study of enzastaurin in second- or third-line treatment of non-small cell lung cancer (NSCLC). Abstract # 7543. American Society of Clinical Oncology (ASCO) Annual Meeting 2007.