Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment

Inclusion criteria * Be willing and able to provide written informed consent for the trial. * Be at least 18 years of age on the day of signing informed consent. * Have a histologically or cytologically confirmed diagnosis of Stage IV metastatic lung adenocarcinoma (AJCC version 8) with mutation analysis by next generation sequencing (NGS) confirming KRAS mutation either at time of diagnosis or at progression on first line treatment. * Have progressed on or intolerant of standard of care first-line treatment with anti-programmed death-ligand 1 (PD1) checkpoint inhibitor monotherapy or anti-PD1 checkpoint inhibitor in combination with platinum doublet chemotherapy for Stage IV metastatic lung adenocarcinoma. The last cycle of first-line treatment must occur at least 28 days prior to administration of trial drugs (i.e., washout period) * Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesion. * Have a life expectancy of at least 3 months. * Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. * Have adequate organ function as indicated by the following laboratory values in Table 1. Specimens must be collected within 14 days prior to the start of trial. * Patient must be willing and able to provide blood samples (12 green tops tubes, roughly 100mL) at the time points indicated in the Study Calendar. * Patient must be willing and able to have core needle biopsies (Goal 4-8 biopsies, final number to be determined by the surgeon and radiologist performing the procedure as safe) of tumor prior to initiation of study drug, and at time points indicated in the Study Calendar. * Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and following completion of therapy for 5 months if female and 7 months if male. * Female subjects of child-bearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Exclusion Criteria * Patients may not be receiving any other investigational agents. If received as part of first line treatment, last administration of previous investigational agent must be greater than 4 weeks prior to administration of study drug combination. * Patients must not be pregnant or nursing due to the potential for congenital abnormalities or harm to nursing infants. * Tumor harbors an epidermal growth factor receptor (EGFR) sensitizing (activating) mutation or an anaplastic lymphoma kinase (ALK) translocation. All other co-mutations will be allowed. * Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are without evidence of progression for at least 4 weeks by repeat radiological imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study drug. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded. * Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable. * Has a known additional malignancy that is progressing and/or required active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical or anal cancer, prostate cancer on stable dose of hormonal therapy without rising prostate-specific antigen (PSA), and breast cancer whom have been treated with curative intent, who may be on hormonal therapy. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator. * HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \<350 cluster of differentiation 4 (CD4+) T cells/microliter in the peripheral blood. No HIV testing is required. * History of allogeneic hematopoietic cell transplantation or solid organ transplantation. * Receipt of a live vaccine within 30 days of planned start of study medication * History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immunosuppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted. * Prisoners or subjects who are involuntarily incarcerated. * Subjects who are compulsorily detained for treatment of either psychiatric or physical (e.g. infectious disease) illness.