Lindsey Rolfe at Clovis Oncology outlines a New Preclinical Data on ALKS 4230 in Combination With Lucitanib
The research assessed the antitumor efficacy and mechanism of action of mALKS 4230, ALKS 4230 mouse ortholog, and lucitanib as monotherapy in conjunction with a preclinical syngeneic colon cancer mouse model. The combination of mALKS 4230 and lucitanib resulted in a dose-dependent, long-lasting complete response (absence of any detectable tumor) and improved survival compared to treatment with mALKS 4230 and lucitanib monotherapy.
The main findings set out in the poster include:
In the group that received the higher dose of mALKS 4230 (out of two doses tested) combined with lucitanib, 100 percent of the treated mice exhibited complete tumor regression and re-challenge protection from new tumor growth, an indication of the immunological memory formation.
The combination of mALKS 4230 with lucitanib resulted in an increase in intratumoral immune cells including CD8 + T cells and dendritic cells relative to treatment with monotherapy, improvements consistent with anti-tumor immune responses.
Combining mALKS 4230 with lucitanib has resulted in a distinct gene expression profile consistent with anti-tumor activity, including enhanced immune cytolytic gene expression with reduced gene expression with pro-angiogenic functions.
Around ALKS 4230 42304
ALKS 4230 is an investigational, novel, engineered fusion protein consisting of modified interleukin-2 (IL-2) and a high affinity IL-2 alpha receptor chain, designed to selectively expand tumor-killing immune cells while preventing the activation of immunosuppressive cells by binding preferentially to the IL-2 receptor complex of intermediate affinity. ALKS 4230 selectivity is designed to exploit the proven anti-tumor effects of current IL-2 therapy while at the same time minimizing certain limitations.
Lucitanib is an oral, active inhibitor of tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor alpha and beta receptors (PDFGRα / β), and fibroblast growth factor receptors 1 through 3 (FGFR1-3). Emerging clinical findings are supporting the combination of angiogenesis inhibitors and immunotherapy to improve efficacy in several indications of cancer. Angiogenic factors, such as vascular endothelial growth factor ( VEGF), are often upregulated in tumors and establish a microenvironment for immunosuppressive tumors. This immunosuppression is reversed with the use of antiangiogenic drugs and can improve immunotherapy responses.
Lucitanib is a prescription product that is unlicensed.
Alkermes plc is a fully integrated , global biopharmaceutical company which develops innovative neuroscience and oncology medicines. The company has a portfolio of addiction and schizophrenia patented commercial drugs and a pipeline of product candidates in development for schizophrenia, bipolar I disorder, neurodegenerative diseases and cancer. Alkermes plc, which is headquartered in Dublin , Ireland, has an R&D center in Waltham, Massachusetts; a research and development facility in Athlone, Ireland; and a production facility in Wilmington, Ohio. For more information please visit the website of Alkermes at www.alkermes.com.
About Oncology by Clovis
Clovis Oncology, Inc. is a biopharmaceutical company focusing on the acquisition, production and commercialization in the U.S. , Europe and other foreign markets of novel anti-cancer agents. Clovis Oncology targets development initiatives for particular subsets of cancer populations and, at the same time, develops diagnostic tools with collaborators that are intended to guide an evolving compound to the population most likely to benefit from its use. Clovis Oncology is located in Boulder, Colorado, and for more information, including additional office locations in the U.S. and Europe, please visit www.clovisoncology.com.
Note from Alkermes concerning forward-looking statements
Such statements set out in this press release constitute "forward-looking statements" within the context of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements on the potential therapeutic benefit of ALKS 4230, as a monotherapy or in combination. You are warned that forward-looking statements are necessarily ambiguous. Although the company assumes that such statements are based on fair assumptions within the limits of its business and operating experience, forward-looking statements are neither assurances nor guarantees, and are inherently subject to a high degree of uncertainty or risk. Owing to numerous hazards and uncertainties, actual results can vary materially from those stated or implied in the forward-looking statements. These threats and uncertainties include, but are not limited to, preclinical and provisional, interim or final clinical results for ALKS 4230 — whether as a monotherapy or in combination — predicting future evidence from the same trials, results from future clinical studies or real-world outcomes; whether ALKS 4230, either as a monotherapy or in combination, may prove dangerous or ineffective; Securities and Exchange Commission (SEC), which is available at www.sec.gov on the SEC website.