Testing the SurVaxM Vaccine for Lung Cancer Prevention

This phase II trial tests how well a survivin peptide vaccine called SurVaxM works in preventing lung cancer in high risk patients. Upon administration, the SurVaxM vaccine activates the immune system to produce an immune cell response against cancer cells that express a protein called survivin. This may result in decreased tumor cell proliferation and lead to tumor cell death. SurVaxM is given with montanide, a substance that helps the immune system respond to the SurVaxM vaccine, followed by sargramostim, which is given to increase the number of white blood cells in the body. The SurVaxM vaccine may help the body make special proteins called antibodies, which may be helpful in preventing the development of lung cancer.

PRIMARY OBJECTIVE: I. To evaluate the effect of SVN53-67/M57-KLH peptide vaccine (SurVaxM) administration on the generation of a systemic anti-survivin immune response. SECONDARY OBJECTIVES: I. To assess the proportion of participants needing a 3-month booster dose to achieve seroconversion. II. To assess the proportion of participants mounting a cellular immune response to SurVaxM vaccination. III. To assess the safety profile of SurVaxM administration in this population. EXPLORATORY OBJECTIVES: I. To associate participants' demographic and clinical characteristics with outcomes (seroconversion or needing the 3-month booster). II. Correlation of human leukocyte antigen (HLA) typing and the association of HLA types to humoral and/or cellular responses. OUTLINE: Patients receive SurVaxM with montanide ISA 51 VG (montanide) subcutaneously (SC) followed by sargramostim SC on day 0, week 2, week 4, and week 6. Patients then receive a booster dose of SurVaxM with montanide SC followed by sargramostim SC on week 18. Patients also undergo collection of blood samples throughout the trial. After completion of study intervention, patients are followed up at weeks 20 and 24.

Inclusion Criteria: * Former and current smokers (male and female) with a \>= 20 pack year smoking history * Prostate, Lung, Colorectal and Ovarian (PLCO)m2012 Lung Cancer Risk Prediction Score \> 1.34% * Participants \>= 18 years old will be enrolled. Because no dosing or adverse event (AE) data are currently available on the use of SurVaxM in participants \< 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 60%) * Platelets \>= 100,000/microliter * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) * Note: Higher total bilirubin levels (=\< 3 mg/dL) can be allowed if due to known benign liver condition, i.e. Gilbert's * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal * Serum creatinine =\< 1.5 x institutional upper limit of normal * The effects of SurVaxM plus montanide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * History of autoimmune disease necessitating systemic immunosuppression, immunodeficiency, and/or organ allograft * Participants may not be receiving any other chemotherapy (except hormonal agents), immunotherapy or investigational agent, or any immunosuppressive agent, including systemic steroids, including those given after organ transplant * Participants with current or prior malignancy except for the following: * Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years before screening and felt to be at low risk for recurrence by treating physician * Adequately treated carcinoma-in-situ or basal cell carcinoma of the skin without current evidence of disease * Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer * Prior or current malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (e.g., localized prostate cancer) may be included * History of allergic reactions attributed to compounds of similar chemical or biologic composition to montanide or granulocyte-macrophage colony-stimulating factor (GM-CSF) * Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study because of the unknown effects of SurVaxM plus montanide on the fetus. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with SurVaxM plus montanide, breastfeeding should be discontinued if the mother is treated with SurVaxM plus montanide * Individuals participating in another interception trial with an immunomodulatory agent will be excluded from participation in this trial for a washout period of 6 months