sirolimus and durvalumab for the treatment of stage i-iiia non-small cell lung cancer

Conditions: Lung Non-Small Cell Carcinoma; Stage I Lung Cancer AJCC v8; Stage IA1 Lung Cancer AJCC v8; Stage IA2 Lung Cancer AJCC v8; Stage IA3 Lung Cancer AJCC v8; Stage IB Lung Cancer AJCC v8; Stage II Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8; Stage IIB Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8

Summary: this trial studies the side effects of sirolimus and durvalumab and to see how well they work in treating patients with stage i-iiia non-small cell lung cancer. sirolimus is an oral medication that blocks the mtor cellular pathway which may help the immune system work better. immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. giving sirolimus before durvalumab may help the immune system get rid of cancer.

primary objectives: i. to evaluate the safety and tolerability of sirolimus followed by durvalumab as neoadjuvant treatment ii. to evaluate the efficacy of sirolimus followed by durvalumab as neoadjuvant treatment for stage i, ii, and iiia non-small cell lung cancer (nsclc) secondary objectives: i. to evaluate the efficacy of sirolimus in combination with durvalumab as neoadjuvant treatment for stage i, ii, and iiia nsclc ii. to evaluate response to sirolimus in combination with durvalumab in patients with pd-l1-positive versus (vs.) pd-l1-negative tumors iii. to evaluate the association between blood mutation burden and response to sirolimus and durvalumab exploratory objectives: i. to evaluate the immune-mediated effects of combination sirolimus and durvalumab ii. to investigate tumor and immune microenvironment changes in tissue samples outline: patients receive sirolimus orally (po) once daily (qd) on days 1-21 in the absence of disease progression or unacceptable toxicity. starting on day 22, patients receive durvalumab intravenously (iv) over 1 hour. treatment with durvalumab repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. within a 2-3 week period after the second dose of durvalumab, but not earlier than two weeks after the administration of durvalumab, patients undergo standard of care surgery. after completion of study treatment, patients are followed up every 3 months for 2 years.

Eligibility criteria:
inclusion criteria: * patients with pathologically documented nsclc: stage i, ii, iiia nsclc based on 8th edition of american joint committee on cancer (ajcc) non-small cell lung cancer staging system * capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (icf) and in this protocol. written informed consent and any locally required authorization (eg, health insurance portability and accountability act in the united states \[us\]) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations * eastern cooperative oncology group (ecog) performance status of 0 or 1 * life expectancy of \>= 26 weeks * body weight \> 30 kg * hemoglobin \>= 9.0 g/dl * absolute neutrophil count (anc) 1.5 x 10\^9/l (\>= 1500 per mm\^3) * platelet count \>= 100 x 10\^9/l (\>= 100,000 per mm\^3) * serum bilirubin =\< 1.5 x institutional upper limit of normal (uln) * aspartate aminotransferase (ast) (serum glutamic-oxaloacetic transaminase \[sgot\])/alanine aminotransferase (alt) (serum glutamate pyruvate transaminase \[sgpt\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\< 5 x uln * measured creatinine clearance (cl) \> 40 ml/min or calculated creatinine cl \> 40 ml/min by the cockcroft-gault formula (cockcroft and gault 1976) or by 24-hour urine collection for determination of creatinine clearance * evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. the following age-specific requirements apply: * women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) * patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up * patients must consent to pre-treatment research biopsy and study peripheral blood collection * patients must have measurable disease, defined by recist v 1.1 * patient is able to take oral medications * patient consents to heavy water (d2o) self-administration if on optional heavy water labelling study exclusion criteria: * patients who have had prior therapy for lung cancer including chemotherapy, hormonal therapy, or radiotherapy * concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study * prior treatment with anti-pd-1, anti-pdl-1, other pd-1/pdl-1 pathway targeting agents, or mtor inhibition * history of allogenic organ transplantation * active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or crohn's disease\], systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome \[granulomatosis with polyangiitis, graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). the following are exceptions to this criterion: * patients with vitiligo or alopecia * patients with hypothyroidism (e.g., following hashimoto syndrome) stable on hormone replacement * any chronic skin condition that does not require systemic therapy * patients without active disease in the last 5 years may be included but only after consultation with the study physician * patients with celiac disease controlled by diet alone * uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (aes) or compromise the ability of the patient to give written informed consent * history of another primary malignancy except for * malignancy treated with curative intent and with no known active disease \>= 5 years before the first dose of investigational product (ip) and of low potential risk for recurrence * adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * adequately treated carcinoma in situ without evidence of disease * qt interval corrected for heart rate using fridericia's formula (qtcf) \>= 470 ms. patient safety and the cardiac skg should be consulted as needed * history of active primary immunodeficiency * active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[tb\] testing in line with local practice), hepatitis b (known positive hepatitis b virus \[hbv\] surface antigen \[hbsag\] result), hepatitis c. patients with a past or resolved hbv infection (defined as the presence of hepatitis b core antibody \[anti-hbc\] and absence of hbsag) are eligible. patients positive for hepatitis c virus (hcv) antibody are eligible only if polymerase chain reaction is negative for hcv ribonucleic acid (rna) * current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. the following are exceptions to this criterion: * intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[ct\] scan premedication) * receipt of live attenuated vaccine within 30 days prior to the first dose of ip. note: patients, if enrolled, should not receive live vaccine whilst receiving ip and up to 30 days after the last dose of ip * female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy * known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients * prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment * patients with a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (ct) scan * inability to stop prohibited concomitant medications * judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements