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

• ClinicalTrials.gov Identifier: NCT03656627
• Recruitment Status: Recruiting
• First Posted: September 4, 2018
• Last Update Posted: June 4, 2020
• Sponsor: Alliance Foundation Trials, LLC.
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Alliance Foundation Trials, LLC.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Autoimmune Diseases; Non-small Cell Lung Cancer; Rheumatoid Arthritis; Psoriasis; Giant Cell Arteritis; Polymyalgia Rheumatica; Systemic Lupus Erythematosus; Crohn Disease; Multiple Sclerosis; Ulcerative Colitis	Drug: Nivolumab	Phase 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety, Activity, and Pharmacology of Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease
• Actual Study Start Date: June 27, 2019
• Estimated Primary Completion Date: October 31, 2022
• Estimated Study Completion Date: October 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nivolumab: Autoimmune Diseases Cohort 1; 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; 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.
Experimental: Nivolumab: Autoimmune Diseases Cohort 2; 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; 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Director of Project Management; 617-525-8627; info@alliancefoundationtrials.org

Locations

United States, Illinois

University of Chicago Medical Center; Recruiting

Chicago, Illinois, United States, 60637

Contact: Christine Bestvina, MD

United States, Massachusetts

Massachusetts General Hospital; Not yet recruiting

Boston, Massachusetts, United States, 02114

Contact: Rebecca Heist, MD, MPH

United States, Michigan

St. Joseph Mercy Hospital; Not yet recruiting

Ann Arbor, Michigan, United States, 48106

Contact: Phillip J Stella, MD

United States, Minnesota

Metro Minnesota Community Oncology Research Consortium; Active, not recruiting

Saint Louis Park, Minnesota, United States, 55416

United States, New Hampshire

Dartmouth Hitchcock Norris Cotton Cancer Center; Recruiting

Lebanon, New Hampshire, United States, 03756

Contact: Konstantin H Dragnev, MD

United States, New Jersey

Atlantic Health System/Morristown Medical Center; Not yet recruiting

Morristown, New Jersey, United States, 07962

Contact: Missak Haigentz Jr., MD

United States, North Carolina

Duke University Medical Center; Active, not recruiting

Durham, North Carolina, United States, 27710

United States, Ohio

The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic; Active, not recruiting

Columbus, Ohio, United States, 43210

United States, Oregon

Providence Cancer Institute Franz Clinic; Recruiting

Portland, Oregon, United States, 97213

Contact: Rachel Sanborn, MD

United States, Pennsylvania

UPMC Hillman Cancer Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contact: Liza Villaruz, MD

United States, Wisconsin

University of Wisconsin Clinical Science Center; Active, not recruiting

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Alliance Foundation Trials, LLC.

Bristol-Myers Squibb

More Information

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• Responsible Party: Alliance Foundation Trials, LLC.
• ClinicalTrials.gov Identifier: NCT03656627
• Other Study ID Numbers: AFT-42
• First Posted: September 4, 2018
• Last Update Posted: June 4, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alliance Foundation Trials, LLC.:

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Arthritis; Arthritis, Rheumatoid; Polymyalgia Rheumatica; Crohn Disease; Colitis; Colitis, Ulcerative; Multiple Sclerosis; Giant Cell Arteritis; Arteritis; Psoriasis; Lupus Erythematosus, Systemic; Autoimmune Diseases; Sclerosis; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Joint Diseases; Musculoskeletal Diseases; Pathologic Processes; Rheumatic Diseases; Connective Tissue Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS