Sapanisertib and Nivolumab for the Treatment of Stage I-IV Non-small Cell Lung Cancer in Patients Who Have Progressed on Prior PD-1/PD-L1 Inhibitor Therapy, I-OVERCOME Study

Exclusion Criteria

• •Histology other than non-small cell lung cancer
• •Central nervous system (CNS) metastasis that is symptomatic and uncontrolled
• •Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• •Presence of an EGFR, ALK, and ROS1 alteration
• •Current systemic anti-cancer treatment other than the study agents, including other investigational agents
• •Previous toxicity that led to permanent and indefinite discontinuation of prior immunotherapy
• •Toxicity from prior immunotherapy required the use of additional immunosuppression other than corticosteroids for management of the AE
• •Experienced recurrence of grade \>= 3 immune-related AE if re-challenged with immunotherapy. Patients with endocrine immune-related AE of =\< grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy
• •Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• •Known human immunodeficiency virus infection
• •Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
• •Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• •Concurrent malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• •Breast feeding or pregnant women
• •Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors
• •Current or prior use of immunosuppressive medication within 28 days before cycle 1 of study treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• •Active or prior documented autoimmune disease within the past 2 years
• •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or pneumonitis
• •Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of sapanisertib. In addition, patients with enteric stomata are also excluded
• •Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fredericia (QTcF) prolongation \> 480 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome or torsade de pointes
• •History of any of the following within the last 6 months before administration of the first dose of the drug:
• •* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
• •* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
• •* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
• •* Placement of a pacemaker for control of rhythm;
• •* New York Heart Association (NYHA) class III or IV heart failure
• •* Pulmonary embolism
• •Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment and patients must have recovered from any effects of any major surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable
• •Uncontrolled illness including, but not limited to, ongoing or active infection, seizures, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, pulmonary hypertension, uncontrolled asthma or oxygen (O2) saturation =\< 90% by arterial blood gas analysis or pulse oximetry in room air, cardiac valve disease, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• •Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study
• •Patients who are taking proton pump inhibitors (PPIs) within 7 days of the first dose of study drug or who require treatment with PPIs throughout the trial or those who are taking H2 receptor antagonists within 24 hours of the first dose of study drug
• •Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing two highly effective methods of birth control
• •Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
• •Known allergy or hypersensitivity to nivolumab, sapanisertib or any excipients