Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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