The purpose of this study is to test if cetuximab (Erbitux) can shrink lung cancers that initially became smaller after taking erlotinib and then started to get bigger despite continuing treatment. Cetuximab is a medicine approved by the U.S. Food and Drug administration for treatment of head and neck and colon cancer. The goal of the phase I portion of this trial is to find out the highest dose of cetuximab that can be taken together with erlotinib. This study will also give an idea of how well cetuximab shrinks lung cancer when given with erlotinib.

The purpose of this study is to test if cetuximab (Erbitux) can shrink lung cancers that initially became smaller after taking erlotinib or gefitinib and then started to get bigger despite continuing treatment. Cetuximab is a medicine approved by the U.S. Food and Drug administration for treatment of head and neck and colon cancer. The goal of this phase is to determine if cetuximab given with erlotinib causes lung cancers to shrink in size.

Inclusion Criteria:

• Pathologic evidence of lung adenocarcinoma confirmed at MSKCC
• Measurable (RECIST) indicator lesions not previously irradiated
• Radiographic progression by RECIST during treatment with erlotinib
• Received treatment with erlotinib throughout the one month prior to enrollment
• Received treatment with erlotinib for >3 months
• At least one of the following:
• Previously received treatment with erlotinib, gefitinib, or an investigational EGFR TK inhibitor (patients may have received other treatments subsequently including radiation or chemotherapy) and had a radiographic partial or complete response to treatment as defined by RECIST criteria
• A documented mutation in EGFR exons 19 or 21.
• Karnofsky performance status ≥ or = to 70%
• Total bilirubin: within normal institutional limits. AST/(SGOT)/ALT(SGPT)< or = to 2.5 X institutional upper limit of normal (ULN)
• Signed informed consent
• Effective contraception *
• Age > 18 years old *Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. All WOCBP MUST have a negative pregnancy test within two weeks prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.

Exclusion Criteria:

• CNS lesions which are symptomatic and/or requiring escalating doses of corticosteroids.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Prior cetuximab or panitumumab. Prior severe infusion reaction to a monoclonal antibody.
• Current grade 2 or greater skin toxicity on erlotinib therapy
• Radiotherapy ≤ or = to 14 days prior to enrollment
• Any investigational agent or therapy ≤ or = to 30 days before enrollment
• Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (except erlotinib) ≤ or = to 30 days before enrollment
• Women who are pregnant or lactating.
• Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection
• Major surgery within 28 days or minor surgery within 14 days of study enrollment
• Men or women of child-bearing potential (women who are post-menopausal < 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception (per institutional standard of care) during the course of the study and after the last investigational product(s) administration (24 weeks for women, 4 weeks for men)