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

NCT03656627 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AFT-42
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 9

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Response Rate

  48 Months

• Progression-Free Survival

  48 Months

• Overall Survival

  48 Months

Study Arms (2)

Nivolumab: Autoimmune Diseases Cohort 1

EXPERIMENTAL

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: Autoimmune Diseases Cohort 2

EXPERIMENTAL

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

Interventions

Nivolumab DRUG

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.

Nivolumab: Autoimmune Diseases Cohort 1; Nivolumab: Autoimmune Diseases Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (9)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Dartmouth Hitchcock Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic

Columbus, Ohio, 43210, United States

Location

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

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MeSH Terms

Conditions

Autoimmune Diseases; Carcinoma, Non-Small-Cell Lung; Arthritis, Rheumatoid; Psoriasis; Giant Cell Arteritis; Polymyalgia Rheumatica; Lupus Erythematosus, Systemic; Crohn Disease; Multiple Sclerosis; Colitis, Ulcerative

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Immune System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Papulosquamous; Skin Diseases; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Muscular Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: September 4, 2018
• Study Start: June 27, 2019
• Primary Completion: March 18, 2021
• Study Completion: March 18, 2021
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)