The main objective of this study is to determine recommended phase II dose and safety of tetrathiomolybdate (TM) in combination with carboplatin and pemetrexed in chemo-naive metastatic or recurrent non-squamous non-small cell lung cancer.

Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer. Previous studies suggest that reduced tumor platinum levels may significantly contribute to platinum resistance and thus poor outcome following platinum-based chemotherapy in lung cancer.

Tetrathiomolybdate (TM) is a fast-acting copper chelator that has been under significant investigation as an anti-cancer strategy due to its anti-angiogenic property. Furthermore, more recent preclinical evidence suggests that combining TM with platinum drugs resulted in higher intratumoral platinum concentration and greater tumor response. The oncologists at the University of Rochester are studying addition of TM to commonly used 1st line platinum-based doublet, carboplatin/pemetrexed, in patients with non-squamous non-small cell lung cancer.

Inclusion Criteria:

>18 years old Performance status 0-1 Newly diagnosed stage IV non-squamous non-small cell lung cancer or recurrent disease after prior surgery and/or irradiation Patients must not have received prior chemotherapy for any stage non small cell lung cancer Brain metastases allowed provided they have been controlled for ≥ 2 weeks after completion of treatment and remain asymptomatic while off corticosteroids for at least 1 day Patient or primary care taker must be informed of and understand the investigational nature of this study and must sign and give written approved informed consent in accordance with institutional guidelines.

If patient is of childbearing potential, she or he must agree to practice an effective method of birth control prior to study entry, for the duration of study participation, and for 30 days after the last study dose.

Patient has adequate organ functions: serum bilirubin ≤ 2.0 mg/dL; alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), or ALT ≤ 5 x ULN if the patient has hepatic metastasis; serum creatinine ≤ 1.5 mg/dL or a calculated creatinine clearance of at least 60 mL/min.

Patient has adequate bone marrow reserve: absolute neutrophil count ≥ 1,500, platelet count ≥ 100,000, and hemoglobin ≥ 9.0.

Exclusion Criteria:

Patient receiving any concurrent chemotherapy Patients who received platinum-based chemotherapy for any purpose Patients who had gastric bypass surgery Patients taking copper supplementation for medical reasons Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk Patients with active and uncontrolled infection Patients with concomitant active malignancy requiring treatment with cytotoxic chemotherapy or radiation therapy (ongoing hormonal therapy for treatment of malignancy would not exclude patients from this trial) Known anaphylactic or severe hypersensitivity to study drugs or their analogs. Patient has failed to recover from any prior surgery within 4 weeks of study entry.

Patient has clinical evidence of copper deficiency (i.e. ceruloplasmin level was less than 15 mg/dL or free serum copper level less than 2.2 g/dL).

Patients with tumors that are epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma receptor tyrosine kinase (ALK) positive. If biopsy specimen is insufficient or inadequate for EGFR and/or ALK testing, subjects are eligible for the study.

Patients who are pregnant or lactating.