Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Safety, Activity, and Pharmacology of Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease

Conditions
-----------------
Psoriasis, Crohn Disease, Autoimmune Diseases, Non-small Cell Lung Cancer, Rheumatoid Arthritis, Giant Cell Arteritis, Polymyalgia Rheumatica, Systemic Lupus Erythematosus, Multiple Sclerosis, Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: Nivolumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Metastatic, locally advanced or recurrent NSCLC, not amenable to curative therapy. 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. 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 No limit on number of prior therapies Ability to provide written, informed consent 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 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 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. Non-pregnant and non-nursing. 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. 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: 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. All adverse events (other than alopecia) from prior therapy must be resolved to Grade 1 or less. 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. 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 No active interstitial lung disease (ILD) or pneumonitis, or a history of ILD or pneumonitis requiring treatment with corticosteroids No live vaccine within 30 days of start of study treatment No carcinomatous meningitis or untreated CNS metastases 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 No other active malignancy 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 No active unstable angina and/or congestive heart failure, or myocardial infarction within 6 months prior to protocol participation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab: Autoimmune Diseases Cohort 1<br>Arms determined by autoimmune type. First cohort consists of patients with: Rheumatoid arthritis, psoriasis, giant cell arteritis/polymyalgia rheumatica, systemic lupus erythematosis If a patient has more than one autoimmune condition, if all the conditions are within either cohort 1 or 2 above, the patient will be assigned to that cohort. If the patient has conditions from both cohort 1 and 2, the patient will be grouped in cohort 2. | Drug: Nivolumab<br>* Nivolumab will be given as an IV infusion 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. 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.<br>|
| Experimental: Nivolumab: Autoimmune Diseases Cohort 2<br>Arms determined by autoimmune type. Second cohort consists of patients with: Other autoimmune diseases (ulcerative colitis, Crohn's disease, multiple sclerosis). Patients must be discussed with PI prior to enrollment. If a patient has more than one autoimmune condition, if all the conditions are within either cohort 1 or 2 above, the patient will be assigned to that cohort. If the patient has conditions from both cohort 1 and 2, the patient will be grouped in cohort 2. | Drug: Nivolumab<br>* Nivolumab will be given as an IV infusion 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. 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicity (DLT) | The DLT determination period is the first six weeks after cycle 1 day 1. Dose limiting toxicities are further defined in the trial protocol. | 48 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence | 48 Months | 
| Progression-Free Survival | Progression-free survival will be evaluated for each cohort using Kaplan-Meier estimator. | 48 Months | 
| Overall Survival | Overall survival will be evaluated for each cohort using Kaplan-Meier estimator. | 48 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Crohn Disease, Opdivo, Autoimmune Diseases, Non-small Cell Lung Cancer, Ulcerative Colitis, Multiple Sclerosis, Systemic Lupus Erythematosus, Polymyalgia Rheumatica, Giant Cell Arteritis, Psoriasis, Rheumatoid Arthritis, Nivolumab