Pfizer Oncology announced today that it will present new data from the company's pipeline, including two novel, dual PI3K/mTOR (phosphatidylinositol 3-kinase / mammalian target of rapamycin) inhibitors (PF-04691502 and PKI-587, also known as PF-05212384); crizotinib (PF-02341066), an ALK (anaplastic lymphoma kinase) inhibitor that also inhibits c-MET (c-mesenchymal-epithelial transition factor); and PF-04605412, an anti-α5β1 inhibitor. Data from these, and other investigational compounds, including sunitinib, axitinib, and figitumumab, will be presented at the American Association for Cancer Research (AACR) 101st Annual Meeting 2010 in Washington, D.C., from April 17 through April 21.
“Pfizer's data at AACR demonstrate our strategic focus on the discovery and development of novel mechanisms that align complex biology with creative clinical strategies”
"Pfizer's data at AACR demonstrate our strategic focus on the discovery and development of novel mechanisms that align complex biology with creative clinical strategies," said Dr. Neil Gibson, chief scientific officer of Pfizer's Oncology Research Unit. "Our research on the mutations and pathways that are genetic drivers of the segments of disease, defined by specific 'genetic signatures,' is designed to help us identify patient populations that will derive the most benefit from the novel therapeutic modalities we discover and develop."
On Sunday, April 18, Pfizer Oncology researchers and leadership will host a media briefing to provide a high-level overview of Pfizer's novel research at AACR. The briefing, "An 'Inside Look' at Early Clinical Development at Pfizer," will be held at The Renaissance Hotel, Room 2, from 7:00 - 8:00 p.m.
Seven Abstracts Presented on New Agents in an Emerging Class
The PI3K pathway and key kinases within it, such as mTOR, are believed to play a central role in regulating cellular signaling that may influence cancer cell growth and survival. Genetic abnormalities in the pathway have been closely linked to the development and progression of cancer.
Pfizer has two dual PI3K/mTOR inhibitors in development, one administered orally (PF-04691502) and one intravenously (PKI-587/PF-05212384). PF-04691502 will be featured during an oral presentation at AACR (Abstract #5779, April 21), providing details that led to the discovery of this selective compound.
An additional six abstracts on PF-04691502 and PKI-587/PF-05212384 will be presented at the meeting (Abstract #s 302, 4473, 4479, 3224, 3492 and 723). Based on these preliminary studies, trials are underway to assess safety and tolerability of these agents in cancer patients with solid tumors.
Pfizer's First-In-Class Agents: Crizotinib (PF-02341066) and PF-04605412
Scientific advances in personalized medicine have led to the identification of ALK as a new therapeutic target in cancer. Crizotinib (PF-02341066) is a first-in-class investigational, oral ALK inhibitor which also inhibits c-MET. The fusion gene EML4-ALK is thought to be a key driver of lung tumorigenesis, and is estimated to be present in approximately 40,000 patients worldwide with newly diagnosed non-small cell lung cancer (NSCLC) annually. A pharmacokinetic and pharmacodynamic (QTc) population analysis from an open label, multi-center Phase 1 dose escalation study in patients with advanced cancer will be presented at AACR (Abstract #1673; April 19).
In addition, various clinical studies suggest the adhesion molecule known as integrin α5β1 plays an important role in cancer progression through the promotion of cancer cell migration, proliferation, survival and metastasis. In lung cancer patients, a five-year survival rate was found to be inversely correlated with the degree of tumor α5 expression, and similar associations have been noted in melanoma and ovarian cancer. Accumulating evidence also suggests that antibody-dependent cellular cytoxicity (ADCC) plays a significant role in anti-cancer therapy. At AACR, Pfizer will present data on PF-04605412, a first-in-class, selective, fully human anti-α5β1 IgG1 antibody that has been specifically engineered to possess ADCC activity in preclinical models (Abstract #3811, April 20).
Research Presentations on Causes of Drug Resistance and Novel Compounds in Animal Models
- A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells (Abstract #628; April 18)
- Development of a model of acquired resistance to a multi- targeted VEGFR TKI and strategies to target resistance mechanisms through combination (Abstract #387; April 18)
- Establishing patient-derived colorectal cancer stem cell models with PI3CA mutation for the development of inhibitor drugs as targeted therapies (Abstract #4483; April 20)
- Inhibition of tumor malignancy by anti-angiogenic therapies in orthotopic mouse models of hepatocellular carcinoma (Abstract #4177; April 20)
- Effects of a novel PI3 kinase/mTOR inhibitor on proliferation and pAKT signaling in canine lymphoma (Abstract #5043; April 21)
Additional Data Presentations
- Sunitinib in advanced NSCLC: Correlation of circulating biomarkers with clinical outcome (Abstract #4682; April 20)
- Molecular predictors of sensitivity to an IGF-1R inhibitor (figitumumab) in pre-clinical models of lung and colon cancers (Abstract #LB-220; April 20)
- Pharmacogenomic analysis of a Phase 3 trial of gemcitabine plus axitinib versus gemcitabine plus placebo in patients with advanced pancreatic cancer (Abstract #78; April 18)
- An open-label Phase 1 study to evaluate the pharmacokinetics of axitinib (AG-013736) in healthy Chinese volunteers (Abstract #2762; April 19)
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