Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer

Inclusion Criteria:

• Patients can have either histologically confirmed malignancy that is radiologicallyevaluable and metastatic or unresectable, or have a malignancy for which aPD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor typesinclude solid tumors and malignancies in which there is known evidence of clinicalactivity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and DrugAdministration (FDA)-approved for the treatment of melanoma, non-small cell lungcancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC),gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neckcancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and anysolid tumor with microsatellite instability (MSI)-high status confirmed. Patientswith HL are eligible but must follow standard response criteria. Additional tumortypes may be eligible on a case by case basis upon discussion with principalinvestigator (PI). Patients enrolling on the trial for adjuvant use will berestricted to those with histology for which a PD-1/PD-L1 inhibitor has beenapproved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC,cervical cancer, and bladder cancer

• Patients who have previously received other forms of immunotherapy (high-dose [HD]IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokineimmunotherapy for at least 4 weeks before nivolumab administration. Patients whohave received prior anti-CTLA4 will be allowed and the washout period is 6 weeks

• Age >= 18 years; children are excluded from this study but may be eligible forfuture pediatric phase 1 combination trials

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >=

• Life expectancy of greater than 12 weeks

• Leukocytes >= 1,000/mcL

• Absolute neutrophil count >= 500/mcL

• Platelets >= 50,000/mcL

• Total bilirubin =< 2 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional ULN or =< 8 x institutional ULN for patients with livermetastases or an autoimmune disease that is contributing to the elevation of thesevalues

• Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using theCockcroft-Gault formula)

• Human immunodeficiency virus (HIV)-infected patients on effective antiretroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must beundetectable on suppressive therapy if indicated

• If history of hepatitis C virus (HCV) infection, must be treated with undetectableHCV viral load

• Patients with new or progressive brain metastases (active brain metastases) orleptomeningeal disease are eligible if the treating physician determines thatimmediate central nervous system (CNS) specific treatment is not required and isunlikely to be required for at least 4 weeks (or scheduled assessment after thefirst cycle of treatment), and a risk-benefit analysis (discussion) by the patientand the investigator favors participation in the clinical trial

• The effects of nivolumab on the developing human fetus are unknown. For this reason,women of child-bearing potential (WOCBP) and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry and for the duration of study participation. WOCBP receiving nivolumabwill be instructed to adhere to contraception for a period of 5 months after thelast dose of investigational product. Men receiving nivolumab and who are sexuallyactive with WOCBP will be instructed to adhere to contraception for a period of 7months after the last dose of investigational product. Women of childbearingpotential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hoursprior to the start of nivolumab. Women must not be breastfeeding. Women who are notof childbearing potential (i.e., who are postmenopausal or surgically sterile aswell as azoospermic men) do not require contraception. WOCBP is defined as anyfemale who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause isdefined clinically as 12 months of amenorrhea in a woman over 45 in the absence ofother biological or physiological causes. In addition, women under the age of 55must have a documented serum follicle stimulating hormone (FSH) level less than 40mIU/mL. These durations have been calculated using the upper limit of the half-lifefor nivolumab (25 days) and are based on the protocol requirement that WOCBP usecontraception for 5 half-lives plus 30 days, and men who are sexually active withWOCBP use contraception for 5 half-lives plus 90 days. Should a woman becomepregnant or suspect she is pregnant while she or her partner is participating inthis study, she (or the participating partner) should inform the treating physicianimmediately

• Ability to understand and the willingness to sign a written informed consentdocument

• Patients with more than one autoimmune disease are eligible. The treating physicianwould determine which autoimmune disease is dominant and the patient would betreated under that specific cohort

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks fornitrosoureas or mitomycin C) prior to entering the study or those who have notrecovered from adverse events (AEs) due to agents administered more than 4 weeksearlier have not resolved or stabilized. Palliative (limited-field) radiationtherapy (RT) is permitted (2 week washout from start of treatment), if all of thefollowing criteria are met:

• Repeat imaging demonstrates no new sites of bone metastases

• The lesion being considered for palliative radiation is not a target lesion

• Patients with prior therapy with an anti-PD-1 or anti-PD-L1

• Patients with prior allogeneic hematologic transplant

• Patients who are receiving any other anticancer investigational agents

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements