Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease
Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease
The purpose of this study is to explore the safety, tolerability and activity of Nivolumab, a
 PD-1 inhibitor, in cohorts of patients with autoimmune disease. Two cohorts of patients will
 be enrolled, based on autoimmune disease type.

 Patients will be screened within 28 days prior to the start of dosing. Eligible patients will
 be enrolled in either of the two cohorts. Patients will receive treatment every two weeks, in
 an outpatient setting. One cycle is a 28-day period, with Nivolumab given on days 1 and 15 of
 a 28-day cycle. Subjects will be permitted to continue treatment beyond initial RECIST 1.1.
The purpose of this study is to explore the safety, tolerability and activity of Nivolumab, a
 PD-1 inhibitor, in cohorts of patients with autoimmune disease. Two cohorts of patients will
 be enrolled, based on autoimmune disease type as outlined below. Entry into cohorts 1 and 2
 will start simultaneously and enroll independently.

 Cohort 1: Rheumatoid arthritis, psoriasis, giant cell arteritis/polymyalgia rheumatica,
 systemic lupus erythematosis Cohort 2: Other autoimmune diseases (ulcerative colitis, Crohn's
 disease, multiple sclerosis). Patients must be discussed with PI prior to enrollment.

 Patients will be screened within 28 days prior to the start of dosing. Eligible patients will
 be enrolled in either of the two cohorts. Patients will receive treatment every two weeks, in
 an outpatient setting. One cycle is a 28-day period, with Nivolumab given on days 1 and 15 of
 a 28-day cycle. Subjects will be permitted to continue treatment beyond initial RECIST 1.1.
 For each cohort, all patients will be dosed at 240 mg IV. There will be no dose de-escalation
 or escalation from this dose level.

 Participants will be followed with telephone follow up for two years after removal from
 protocol therapy or until death, whichever occurs first. Phone calls will be placed every six
 months and survival follow up obtained. Participants removed from protocol therapy for
 unacceptable adverse event(s) will be followed until resolution or stabilization of the
 adverse event, in addition to the follow up for two years after removal from protocol therapy
 or until death, whichever occurs first.
Inclusion Criteria:

 1. Age > 18

 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

 3. Metastatic, locally advanced or recurrent NSCLC, not amenable to curative therapy.

 4. Patients should have received at least one platinum-based chemotherapy regimen for
 recurrent or metastatic disease or have received platinum-based chemotherapy as part
 of adjuvant or neoadjuvant therapy and experienced progression of disease within 6
 months of completing therapy.

 5. Patients with tumor genetic alterations such as EGFR, ALK, ROS1 or BRAF V600E
 alterations for which there is FDA-approved targeted therapy must have been treated
 with the appropriate targeted inhibitors in prior therapy

 6. No limit on number of prior therapies

 7. Ability to provide written, informed consent

 8. Patients must be on a stable regimen of treatment for their autoimmune condition
 without need for addition of new medications or escalating doses of preexisting
 medications in the previous 12 weeks prior to study entry

 9. In addition, patients with the following autoimmune diseases must have baseline
 disease activity scores as follows (please see Appendix A):

 -  For rheumatoid arthritis: DAS28 < 5.1

 -  For polymyalgia rheumatica: PMR-AS < 17

 -  For Sjogrens: ESSDAI < 14

 -  For ulcerative colitis: SSCAI < 5

 -  For Crohn's disease: CDAI < 450

 -  For systemic lupus erythroderma: SLEDAI-2K < 20

 -  For multiple sclerosis: EDSS < 5.5

 10. Adequate organ and marrow function as defined by:

 -  absolute neutrophil count ≥ 1,500/mcL

 -  platelets ≥ 100,000/mcL

 -  total bilirubin ≤ 2.5 × institutional upper limit of normal

 -  AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal, OR

 -  AST(SGOT)/ALT(SGPT ) ≤5 × institutional upper limit of normal if liver metastases
 are present

 -  Creatinine within normal institutional limits OR

 -  Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
 above institutional normal.

 11. Non-pregnant and non-nursing.

 12. Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth
 control or be surgically sterile, or abstain from heterosexual activity for the course
 of the study through 5 months after the last dose of study medication. Patients of
 childbearing potential are those who have not been surgically sterilized or have not
 been free of menses > 1 year.

 13. Male patients must agree to use an adequate method of contraception starting with the
 first dose of study therapy through 7 months after the last dose of study therapy.

 Exclusion Criteria:

 1. No chemotherapy or radiotherapy within two weeks of study entry. Prior targeted
 therapy is allowed as long as at least 5 half-lives have elapsed since last dose.

 2. All adverse events (other than alopecia) from prior therapy must be resolved to Grade
 1 or less.

 3. Patients who are known to be HIV positive are excluded due to the known immunologic
 alterations associated with the disease. HIV testing is not required.

 4. No uncontrolled intercurrent illness such as active infection, or psychiatric illness
 or social situation that in the judgment of the investigator would limit compliance
 with study requirements

 5. No active interstitial lung disease (ILD) or pneumonitis, or a history of ILD or
 pneumonitis requiring treatment with corticosteroids

 6. No live vaccine within 30 days of start of study treatment

 7. No carcinomatous meningitis or untreated CNS metastases

 8. No history of significant cardiac disease or presence of an abnormality in
 electrocardiograms that, in the investigator's opinion, is medically exclusionary or
 clinically meaningful

 9. No other active malignancy

 10. No known history of or positivity for active hepatitis B or C. HBV DNA and/or HCV RNA
 must be undetectable and HBsAg must be negative at the time of screening

 11. No active unstable angina and/or congestive heart failure, or myocardial infarction
 within 6 months prior to protocol participation