ARCHER 1009 Study (Advanced Research for Cancer targeted pan-HER therapy): Dacomitinib (PF-00299804), a pan-HER inhibitor, vs Erlotinib in second- or third-line therapy for advanced non- small cell lung cancer (NSCLC)

Dacomitinib (PF-00299804) is an investigational agent and has not been approved for marketing by any regulatory agency at this time.

INTRODUCTION Dacomitinib is an oral, once-daily, pan-HER inhibitor. It is an irreversible inhibitor of HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases.1 Dacomitinib targets multiple receptors of the HER pathway, whereas currently marketed HER-1 (EGFR) inhibitors for non-small cell lung cancer (NSCLC) target only one receptor in this pathway.1

Current drug development against the HER family in NSCLC has been focused mostly on small molecule selective and reversible tyrosine kinase inhibitors (TKIs) and chimeric monoclonal antibodies.

In pre-clinical studies, dacomitinib has been shown to inhibit the signaling in both wild type and mutant HER-1 (EGFR), including forms of NSCLC that are resistant to currently marketed HER-1 (EGFR) inhibitors, such as erlotinib and gefitinib.

RATIONALE Based on the results of an ongoing Phase 2 study (Study A7471028) showing that dacomitinib significantly improved progression-free survival (PFS) and improved lung cancer symptoms compared to erlotinib in patients with advanced NSCLC after chemotherapy failure,2 Pfizer has initiated a Phase 3 study (ARCHER 1009) of dacomitinib versus erlotinib for second-/third-line treatment of advanced NSCLC.3

OBJECTIVES To demonstrate the efficacy and safety of dacomitinib versus erlotinib as a second-/third- line treatment of advanced NSCLC.

The study will be conducted in two co-primary populations: all enrolled patients and enrolled patients with NSCLC confirmed for KRAS wild type.4

3 ENDPOINTS  Primary Endpoint: o Progression-free survival (PFS) per Independent Radiologic Review in the co-primary populations

 Select Secondary Endpoints:3 o Overall survival (adequately powered for OS) o Objective response rate o Duration of response o Safety and tolerability o Patient-reported outcomes

STUDY DESIGN  Phase 3, double-blind, randomized, multinational, multicenter study comparing dacomitinib to erlotinib in two co-primary populations: all enrolled patients and enrolled patients with NSCLC confirmed for KRAS wild type.3,4 o Arm A: Patients will receive dacomitinib 45 mg orally once daily o Arm B: Patients will receive erlotinib 150 mg orally once daily

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3,4 SELECTED  Selected Inclusion Criteria: ELIGIBILITY o Histologically or cytologically proven advanced or metastatic NSCLC CRITERIA o Tumor tissue adequate for biomarker analysis for epidermal growth factor receptor (EGFR) and KRAS status determination o Patients must have received at least one and no more than two systemic therapy regimens (which includes at least one standard chemotherapy for advanced NSCLC) o Eastern Cooperative Oncology Group (ECOG) performance status 0-2 o Adequate renal and hepatic function o Previous, treated brain metastases are allowed if they are neurologically and radiographically stable and patient is off corticosteroids

 Selected Exclusion Criteria:3,4 o Prior therapy with an EGFR TKI or any agent known or thought to act on any of the HER family receptors o Any element of carcinoid or small-cell components in the lung cancer o Active brain metastases or known leptomeningeal disease o Investigational agent-based therapy as only previous treatment for NSCLC o Any clinically significant gastrointestinal disorders that could affect transit or absorption of an oral medication o Known diffuse interstitial lung disease or uncontrolled or significant heart disease o Medications that affect the metabolism of erlotinib

3,4 NUMBER OF  The trial will enroll 800 patients from research sites globally. PATIENTS

For more information about dacomitinib trials currently open and enrolling, please visit www.clinicaltrials.gov or www.pfizercancertrials.com or call Pfizer Oncology’s toll-free number at 1-877.369.9753 (U.S.).

1 Gonzales AJ, Hook KE, Althaus IW et al. Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbBreceptor tyrosine kinase inhibitor. Mol Cancer Ther. 2008;7:1880-89. 2 Ramalingam SS, Boyer MJ, Park K, et al: Randomized phase 2 study of PF299804, an irreversible human epidermal growth factor receptor (EGFR) inhibitor, versus (v) erlotinib (E) in patients (pts) with advanced non-small cell lung cancer (NSCLC) after chemotherapy (CT) failure: quantitative and qualitative benefits. Ann Oncol. 21: 2010 (suppl 8; abstr 365PD) 3 ClinicalTrials.gov. ARCHER 1009: A Phase 3 Study Of PF-00299804, A Pan-HER Inhibitor, Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer . Available at: http://clinicaltrials.gov/ct2/show/NCT01360554. Accessed March 23, 2012. 4 Data on file. Pfizer Inc, New York, NY.

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