New data highlighting Pfizer's approach to cancer drug development to be presented at ASCO meeting

May 21 2010

Pfizer Oncology (NYSE: PFE) will present new data highlighting the company's focused approach to cancer drug development through the identification and validation of molecular targets.  These results will be presented at the 46th Annual American Society of Clinical Oncology (ASCO) meeting in Chicago from June 4-8.  

"Pfizer Oncology is committed to applying discoveries from cancer biology and genetics to the development of new drugs in a focused and rational way.  This approach is being used to study crizotinib (PF-02341066), an ALK inhibitor, in lung cancer patients carrying the ALK fusion gene, and bosutinib, a dual Src and Bcr-Abl kinase inhibitor, in patients with chronic myelogenous leukemia who have progressed despite standard-dose imatinib," said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer's Oncology Business Unit.  "We're also working to apply this personalized approach to better understand how already approved agents, such as Sutent®, may work better in certain patient populations within approved indications." 

Advancing Research and Understanding in NSCLC

Pfizer Oncology has multiple compounds in development to treat the various forms of non-small cell lung cancer (NSCLC).

At ASCO, Pfizer will present updated data from an expansion cohort of a Phase 1/2 study evaluating crizotinib (PF-02341066) in patients with NSCLC carrying the ALK (anaplastic lymphoma kinase) fusion gene.  Alteration of the ALK gene is thought to be a key driver of lung tumorigenesis in a subset of NSCLC patients.  Worldwide, it is estimated that approximately 45,000 newly diagnosed NSCLC patients per year are ALK positive.   These data will be featured in the ASCO Plenary Session on Sunday, June 6 (Abstract #3).

Crizotinib (PF02341066), a first-in-class, oral ALK inhibitor, is currently being evaluated in an open-label randomized Phase 3 trial, known as PROFILE 1007, which compares crizotinib (PF-02341066) with standard of care chemotherapy in the treatment of ALK-positive recurrent NSCLC.  Crizotinib is also being studied in a Phase 2 trial, known as PROFILE 1005, in similar patients who have received more than one line of prior chemotherapy.  Pfizer has partnered with Abbott Molecular to develop a diagnostic to screen patients with NSCLC for the presence of alterations in the ALK gene.

PF-00299804 is an investigational, oral, pan-HER (pan-human epidermal growth factor receptor) inhibitor.  It is an irreversible small molecule inhibitor of HER-1 (EGFR - epidermal growth factor receptor), -2 and -4 tyrosine kinase.  Data from a global, randomized Phase 2 trial evaluating the anti-tumor activity and safety of PF-00299804 compared to erlotinib, in patients with NSCLC following progression on treatment with one or more chemotherapy regimens, will be presented in a poster discussion session (Abstract #LBA7523, June 7).  PF-00299804 is currently being evaluated in BR.26, a Phase 3 double-blind, placebo-controlled, randomized study in patients with stage IIIB/IV NSCLC who have received standard chemotherapy and EGFR inhibitor therapy.  This trial is being led by the National Cancer Institute of Canada (NCIC) - Clinical Trial Group (Kingston, Ontario).  

Pfizer will present results from a Phase 3 trial (A4021016) of figitumumab (CP-751,871), a selective fully human IgG2 monoclonal antibody against the insulin like growth factor 1 receptor (IGF-1R) pathway, in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with NSCLC (Abstract #7500, June 5).  This study was discontinued in December 2009 following the recommendation of an independent Data Safety Monitoring Committee who found that the addition of figitumumab to paclitaxel plus carboplatin would be unlikely to meet the primary endpoint of overall survival compared to paclitaxel plus carboplatin alone.  Pfizer is continuing to analyze the clinical and biomarker data from this and other trials to identify a potential subset of NSCLC patients in whom further evaluation of figitumumab is warranted.  

Additional Research in Identifying Molecular Targets

Bosutinib is an investigational oral dual Src and Bcr-Abl kinase inhibitor.  It is believed that bosutinib may inhibit activated Bcr-Abl in chronic myeloid leukemia (CML) cells that allow the cells to grow, survive and reproduce.

• Phase 2 study of safety and efficacy of bosutinib in patients with Philadelphia chromosome positive chronic phase CML who are resistant to imatinib and other tyrosine kinases (Abstract #6502, June 7)(11)

Bosutinib is currently being evaluated in an ongoing, randomized, open-label, Phase 3 trial which compares bosutinib with standard dose imatinib in patients with previously untreated, chronic phase, Philadelphia chromosome (Ph+) CML.

As part of Pfizer Oncology's commitment to advancing the science of renal cell carcinoma (RCC), Pfizer has partnered with Genomic Health, Inc. a molecular diagnostic company, on the development of a genomic test to estimate the risk of recurrence following surgery for patients with Stage 1-3 clear cell RCC. 

• Identification of prognostic genomic markers in patients with localized clear cell RCC (Abstract #4501, June 5)

Ongoing Evaluation of Sutent (sunitinib malate)

Sutent has played a significant role in advancing treatment for patients with advanced RCC or gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate and remains a standard of care in these indications. Pfizer is continuing to study the potential role of Sutent in the treatment of various solid tumors including advanced NSCLC, advanced castration-resistant prostate cancer,(14) and as adjuvant therapy for RCC, in Phase 3 trials.

• Phase 3 patient-reported outcomes study in patients with pancreatic neuroendocrine tumors (NET) receiving sunitinib (Abstract #4003, June 5)
• Updated efficacy and safety results of the Phase 3 trial of sunitinib versus placebo for the treatment of pancreatic NET (Abstract #4000, June 5)

Analyses of efficacy and safety data from two Phase 3 trials of sunitinib in metastatic/advanced breast cancer will be presented.  Earlier this year Pfizer announced that these studies did not meet their primary endpoints.

• Sunitinib in combination with docetaxel (D) vs D alone for the first-line treatment of advanced breast cancer (ABC) (Abstract #LBA1010, June 8)
• Phase 3 Study of Sunitinib plus Capecitabine in Previously Treated ABC (Abstract # LBA1011, June 8)

Additional Data Presentations

Pfizer will also present data from its development program, including:

• Interim data for ACT III - Phase 2 trial of PF-04948568 (CDX-110)  [an investigational immuno-oncology vaccine targeting the tumor specific EGFR mutant EGFRvIII] in combination with temozolomide in patients with glioblastoma (Abstract #2014, June 5)
• Final report of a phase 1 clinical pharmacokinetic and pharmacodynamic study of PD-00562271 targeting focal adhesion kinase (FAK) in advanced solid tumors (Abstract #3028, June 6)
• Pharmacodynamically guided dose selection of PF-00337210, a VEGFR2 tyrosine kinase inhibitor in a phase 1 study (Abstract #3033, June 6)
• First-in-human dose-escalation safety and PK trial of a novel intravenous humanized monoclonal CovX body inhibiting angiopoietin (Abstract #2524, June 5)

Data on the following compounds and investigational agents will also be presented:  axitinib (RCC), Torisel (RCC), Camptosar® (colorectal cancer), and tremelimumab (melanoma, pancreatic).