The purpose of this study is to test the drug Bortezomib to see how well it works. The investigators want to find out what effects, good or bad, it has on patients with a limited smoking history or who have a specific mutation associated with their lung cancer.

Inclusion Criteria:

• Pathologic or cytologic evidence of non-small cell lung cancer (NSCLC)
• Documented KRAS mutation
• History of smoking < 100 cigarettes (never-smoker) OR patient with a KRAS G12D mutation regardless of smoking history
• Clinical stage IIIB/IV or recurrent/medically inoperable NSCLC
• Age ≥ 18 years
• Three (3) weeks since last chemotherapy, and three (3) weeks since prior radiation therapy and recovered from treatment
• Karnofsky performance status ≥ 70%
• Adequate hematologic, and/or hepatic function WBC ≥ 3,000/ul or absolute neutrophil count ≥ 1,000/ul Hemoglobin ≥ 9.0 g/dl Platelet count ≥ 100,000/ul AST ≤ 2.0 X ULN (upper limit of normal)
• Total bilirubin ≤1.5 x ULN Measurable indicator lesions by RECIST v1.1 criteria.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
• Male subjects must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.

Exclusion Criteria:

• Uncontrolled central nervous system metastases defined as any lesion which is either a. symptomatic, or requiring escalating doses of corticosteroids
• Significant medical history or unstable medical condition such as uncontrolled diabetes myocardial infarction within 6 months prior to enrollment New York Heart Association Class III or IV heart failure severe uncontrolled ventricular arrythmias uncontrolled angina ECG evidence of acute ischemia or active conduction system abnormalities
• Baseline ≥ grade 2 peripheral neuropathy by CTCAE v 4.0 (Appendix B)
• Known hypersensitivity to boron or mannitol
• Female patients who are pregnant/lactating or have a positive serum or urine β-hCG pregnancy test
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• No active concurrent malignancy, with the exception of in-situ malignancy completely resected basal cell carcinoma or squamous cell carcinomas of the skin low-risk prostate cancer after curative therapy
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial

2 years