Patients must not have a history of immune-mediated pneumonitis or colitis that required interruption of therapy or treatment of steroids
Patients with active colitis or immune-mediated colitis that has not resolved to grade 1 or less.
Subjects who experienced immune related pneumonitis, pituitary or thyroid dysfunction, or pancreatitis while on treatment with immuno-oncology agents
Treatment-related, immune-mediated adverse events associated with prior immunotherapeutic agents
Prior history of hypersensitivity, drug or radiation-induced, or other immune-mediated pneumonitis
Active immune-mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis, (non-infectious) pneumonitis.
Participant must not have a prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis while receiving immunotherapy.
Prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis (or any other unresolved or symptomatic adverse event in the last 3 months) while receiving immunotherapy.
History of CTCAE >= grade 2 immune mediated endocrinopathy from prior cancer immunotherapy
Requirement for systemic immune suppressive medication
A life-threatening (Grade 4) immune-mediated adverse event related to prior immunotherapy.
Active colitis or previous immune-mediated colitis that has not resolved to grade 1 or less.
Evidence of other immune related disease /conditions.
Must not have experienced a Grade ?3 immune-related AE or an immune-related neurologic or ocular AE, pneumonitis or cardiomyopathy of any grade while receiving prior immunotherapy.
Patients with prior ? Grade 3, serious, or life threatening immune-mediated reactions following prior anti-PD-1 or other immune-oncology therapies
Participants undergoing active therapy for immune-mediated or infectious colitis upon admission for allogeneic HSCT
Treatment with systemic immune modulators 2 weeks before enrollment (day 1)
Prior immune therapy (e.g. related vaccinia and fowlpox vaccines or antigen-specific peptides) is allowed
Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
History of any of the following toxicities associated with a prior immunotherapy: \r\n* Grade > 3 immune mediated adverse event that was considered related to previous immunotherapy and required immune suppressive therapy\r\n* Immune mediated adverse event that was considered related to previous immunotherapy and is still > grade 1 with immune suppressive therapy
Prior exposure to immune-mediated therapy
History of immune-mediated pneumonitis
History of auto-immune disease (e.g., thyroiditis, lupus), except vitiligo
No active auto-immune disease and not on therapy for auto-immune disease. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible. Patients who have adrenal insufficiency and hypophysitis from prior immunotherapy if they are on stable medical replacement doses are eligible
Use of immune suppressive agents within 30 days
History of grade 3 or higher immune-mediated adverse event (including AST/ALT elevations that where considered drug related and cytokine release syndrome) that was considered related to prior immune-modulatory therapy (e.g., checkpoint inhibitors, costimulatory agents etc.) or any grade immune-related adverse events (AEs) that required immune suppressive therapy
Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of REGN2810, or associated with immune-mediated adverse events that were ? grade 1 within 90 days prior to the first dose of REGN2810, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-40.
History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
IMMUNE RECONSTITUTION STUDY ONLY: Be willing and able to provide written consent/assent for the immune reconstitution portion of the trial only
Has evidence of immune- mediated hepatitis, nephritis, or thyroiditis
Patients that had grade 3/4 immune-related adverse events (AEs) on ipilimumab that required more than 12 weeks of immune suppression with corticosteroids
Patients with history of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis
Must not have experienced a Grade ?3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy.
The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder with the exception of:\r\n* Vitiligo
Concurrent use of systemic immune suppressive other than calcineurin inhibitors and sirolimus
Significant auto-immune disease requiring hospitalization within the past two years or any history of life-threatening auto-immune disease
History of pneumonitis requiring hospitalization or systemic immune suppressive therapy
Prior treatment with immune-modulating agents within 28 days before REGN2810
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nHistory of auto-immune disease requiring steroid maintenance, or history of primary immunodeficiency
History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
Prior auto-immune disease
Patients must not have a history of any immune system disorder, or laboratory abnormality or any condition that could potentially alter immune function
Current use of illicit drugs, glucocorticoids other than those necessary for concurrent radiotherapy, adrenal failure or septic shock, or other immune-suppressing or immune-modulating drugs. Glucocorticoids for anti-emetic prophylaxis and therapy should only be used as a last resort.
Evidence of other immune related disease/conditions.
History of or current immunodeficiency disease or prior treatment compromising immune function
Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
History of auto-immune disease per physician discretion
The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder with the exception of: vitiligo, diabetes or thyroid dysfunction
Patients with active auto-immune disease requiring immunosuppressive medication
For melanoma patients, patients must have received prior programmed cell death protein 1 (PD-1) therapy and have progressed immune-related progressive disease (irPD) by immune-related Response Criteria (irRC)
Patients may not be receiving any steroids or other anti-immune therapy at the time of registration
Prior treatment with other immune modulating agents within fewer than 4 weeks prior to the first dose of REGN2810. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB (CD137), OX-40, therapeutic vaccines, or cytokine treatments.
Relapsed, progressing or persistent malignancy requiring withdrawal of systemic immune suppression.
Patients with active neurological auto immune or inflammatory disorders(e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)
Prior immune-oncology therapy
Prior treatment with an immune-therapy.
Any immunodeficiency disease or immune-compromised state
Use of immune modulators and/or any immunosuppressive drugs.
History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
No prior exposure to immune-mediated therapy,
History of auto-immune disease
Patients with known auto-immune disease
Subject who has active auto-immune disease.
Active auto-immune disease
Any congenital or acquired condition leading to compromised ability to generate an immune response
Requirement for continual immune suppression
A history of any grade immune-related ocular event.
Previously received an immune therapy that was discontinued due to immune-related AEs, regardless of grade.
Prior exposure to immune-mediated therapy
New systemic immune suppressive agent added for the treatment of chronic GVHD within 2 weeks prior to enrollment\r\n* Addition of a new systemic immune suppressive treatment simultaneously with ixazomib is also prohibited
No prior exposure to immune-mediated therapy;
No prior exposure to immune-mediated therapy
Willingness to provide blood samples for immune assessment and other tests
History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy
Prior exposure to selected immune cell-modulating antibody regimens
Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
Active immune-mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis.
Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant
Systemic immune suppression or systemic therapy for cGvHD started within preceding 4 weeks including extracorporeal photopheresis
Auto-immune disease
Subjects with relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
Evidence of immunodeficiency or immune suppression
Active joint inflammation or other immune disorder involving joints (osteoarthritis is not exclusionary)
Active joint inflammation or history of inflammatory arthritis or other immune disorder involving joints
Treatment with immune modulators including
Previous immune-mediated therapy
normal immune function
Acute or chronic viral, bacterial immune or other disease associated with abnormal immune function
Immune suppression
Active known auto-immune disease with the exception of autoimmune thyroiditis, vitiligo, and alopecia;
Documented history of severe autoimmune or immune mediated symptomatic disease that required prolonged (more than 2 months) systemic immunosuppressive (ie, steroids) treatment
Grade 3 immune mediated adverse event that was considered related to previous immunotherapy and required immune suppressive therapy;
Active joint inflammation or history of inflammatory arthritis or other immune disorder involving the joints
Patients must have reached Week 24 of the core protocol in immune-related complete response (irCR), immune-related partial response (irPR), immune-related stable disease (irSD), or immune-related progressive disease (irPD) (unconfirmed) with evidence of tumor inflammatory reaction.
Prior treatment with systemic immune modulating agents (other than anti-PD-1/PD-L1 agents) that was within 28 days prior to enrollment, or within 90 days prior to enrollment if there was an immune related adverse event, or associated with toxicity that resulted in discontinuation of the immune modulating agent
f. Immunologically mediated disease (eg, rheumatoid arthritis, autoimmune hepatitis, immune mediated glomerulonephritis).
Patients with history of autoimmune disease (excluding thyroiditis on chronic thyroid replacement therapy) or active auto-immune disease, due to a risk of exacerbation of autoimmunity with r-hIL7; patients with a history of B cell malignancy due to a risk for growth with rhIL7 therapy
Prior therapy with agents targeting immune coinhibitory receptors.
immunodeficiency, immune compromised state or receiving immunosuppressive therapy
History of immune-mediated pneumonitis
Subject has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
Systemic immune suppression or systemic therapy for cGVHD started within preceding 4 weeks
If participating in optional biospecimen collection; as per self-report, has medical conditions that affect the immune system and would confound immune evaluation (e.g., autoimmune disorder, inflammatory disease; uncontrolled thyroid disease; active infection; myocardial infarction or stroke in the last 6 months; type I diabetes; acute hepatitis; recent vaccination for viral disease)
Immune suppressive medication
Immune compromised or other serious medical conditions, other than cancer diagnostic, at enrollment; immune compromised subjects will be defined as having absolute neutrophil count (ANC) less than 1000 as determined by complete blood count testing (CBD) performed weekly as standard of care in individuals receiving chemoradiation
Other uncontrolled immune-compromising illness
Co-medication that may interfere with study results; e.g., immune-suppressive agents other than corticosteroids
Subject has significant auto-immune disease
Significant auto-immune disease requiring hospitalization within the past two years or any history of life-threatening auto-immune disease
History of pneumonitis requiring hospitalization or systemic immune suppressive therapy
Patient has a compromised immune system or autoimmune disease (WBC < 4000 or > 20,000)
No prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines.
Patient has compromised immune system or autoimmune disease (WBC < 4000 or > 20,000)
Auto-immune disease, which: