Dupilumab with or without Anakinra in Combination with Immunotherapy for the Treatment of Relapsed, Refractory, or Metastatic Non-small Cell Lung Cancer

Inclusion Criteria

• Patients must have a pathologically confirmed diagnosis of NSCLC
• Patients must have progressed (clinically or radiographically) on or following prior therapy with a PD-1 or PD-L1 targeted antibody
• Patients may have only 0 or 1 intervening lines of therapy from the prior PD-(L)1 blocking therapy
• Patient must be willing and able to provide blood samples (12 green-top tubes, roughly 100 mL) at the time points indicated in the study calendar
• Patient must be willing and able to have core needle biopsies, or forceps biopsies if clinically feasible by (goal 3-6 biopsies, final number to be determined by the interventionalist performing the procedure as safe) of tumor prior to initiation of dupilumab and at the on-treatment time point. Should patients undergo pre-treatment or on-treatment biopsy procedure and inadequate number of biopsies are obtained, they may proceed with initiation/continuation of treatment at the discretion of the investigator and treating physician
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) 0-2. The exception will be patients carrying long term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months
• Ability to understand and the willingness to sign a written informed consent
• Absolute neutrophil count (ANC) >= 1,000/mcL
• Platelets >= 75,000/mcL
• Hemoglobin >= 9 g/dL
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >=60 mL/min for patient with creatinine levels > 1.5 X institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 ULN =< 3 X ULN for patients with liver metastases
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X ULN OR =< 5 X ULN for patients with liver metastases
• Albumin >= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless patient is receiving anticoagulant therapy as long as partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 14 days from start of therapy. Washout for palliative radiotherapy is 14 days
• Patients may not be receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (=< 10days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to =< 10 mg prednisone will not be excluded
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
• Human immunodeficiency virus (HIV) positive with detectable viral load, or anyone not on stable anti-viral (highly active antiretroviral therapy [HAART]) regimen, or with < 350 CD4+ T cells/microliter in the peripheral blood. HIV testing is not required for patients with no known history of HIV
• Has known active hepatitis B (e.g., hepatitis B virus [HBV] detected by polymerase chain reaction [PCR] or active hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected). Patients with hepatitis B (hepatitis B surface antigen positive [HepBsAg+]) who have controlled infection (serum hepatitis B virus deoxyribonucleic acid (DNA) PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug
• History of allogeneic hematopoietic cell transplantation or solid organ transplantation
• Receipt of a live vaccine within 30 days of planned start of study medication
• Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps)Principle investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient
• History of immune related adverse event (irAE) in response to prior immunotherapy that has not improved to a grade 0 or 1; this does not include endocrinopathies which can be treated with hormone replacement therapy
• History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted
• Patient has received anakinra in the last 12 months (Cohort B)