According to a 2003 Pharmacor Report on non-small cell lung cancer (NSCLC), the prevalence of Stage III/IV NSCLC is estimated at approximately 220,000 patients in the major pharmaceutical markets of the US, Europe, Japan, and Canada combined, and current therapies achieve less than ten months survival for this group. Because only a minority of patients live for more than one year after diagnosis and the five-year survival rate is less than 15%, NSCLC is characterized by a substantial unmet need for more effective therapies. Accordingly, clinical trials exploring benefits of investigational new drug (IND) strategies are one of the few alternatives to potentially increase survival and/or improve quality of life. The applicant proposes to conduct an IND study in which patients with EGFR-positive, NSCLC who have recurrent, refractory or extensive (metastatic) disease following one prior first-line treatment regimen will be entered into a Phase 1 dose escalation trial consisting of increasing doses of activated T cells (ATC) armed with the bispecific antibody OKT3 (muromonab) x Erbitux (EGFRBi-armed ATC). ATC will be expanded for 14 days from a leukapheresis product of each patient, armed with EGFRBi, cryopreserved, and infused in 8 divided doses. Escalating doses of armed ATC will be given until the maximum tolerated dose (MTD) is determined or the maximum technically attainable dose has been reached. Three patients will be treated at each dose level. Each patient will receive a total of 8 infusions (twice per week for 4 weeks). Patients will also receive low dose subcutaneous Interleukin-2 (IL-2) (300,000 IU/m2/day) and Granulocyte macrophage colony-stimulating factor (GM-CSF) (250 ?g/m2 twice per week), both of which will start 3 days before the first armed ATC infusion and end 7 days after the last dose of armed ATC. The doses of armed ATC will be escalated at the dose levels of 5, 10, 20, and 40 billion armed ATC per infusion. The primary objective of this study is to determine the safety and MTD of EGFRBi-armed ATC that can be administered to patients with advanced NSCLC. Secondary objectives include evaluation of clinical outcomes and characterization of patient anti-NSCLC tumor immunity and immunological responses associated with EGFRBi-armed ATC infusions. A total of 12 to 24 patients will be needed for completion of the Phase 1 study. The applicant hypothesizes that combining patient ATC with Erbitux via the bispecific antibody (BiAb) approach may provide a potent, non-toxic strategy for targeting EGFR-expressing NSCLC that are unresponsive or develop resistance to conventional or other EGFR-targeted therapies.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project (R01)
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Special Emphasis Panel (ZFD1-OPD-L (01))
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Roger Williams Hospital
United States
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