Ipilimumab and Nivolumab in Treating Patients with Recurrent Extensive Stage Small Cell Lung Cancer

Inclusion Criteria

• Signed informed consent
• Ability to comply with protocol
• Age >= 18 years
• Histologically or cytologically documented extensive stage (ES)-SCLC previously treated with at least one regimen, including a platinum containing chemotherapy regimen, with progression of disease on or after their most recent therapy * Patients previously diagnosed with limited stage SCLC treated with concurrent chemoradiation with a platinum doublet now diagnosed with recurrent extensive disease are eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• At least one tumor lesion amenable to incisional, excisional, core or forceps (transbronchial) biopsy. Patients must be willing to undergo tumor biopsies before starting trial therapy and 3 weeks after initiation of therapy * If the initial biopsy will be excisional, the excised tumor cannot be counted as a target lesion and there must be another lesion amenable to incisional, excisional, core or forceps biopsy. In this scenario, the second biopsy can only be excisional if the lesion to be excised is not a target lesion * Cytology tumor specimens (e.g. from fine-needle biopsies, or drainage of pleural/pericardial or ascites fluid) are not acceptable. Biopsies of bone lesions that do not have a soft tissue component are also not acceptable (i.e. decalcified tumor samples are not acceptable). Non-lymph node sites would be biopsied preferentially
• Measurable disease, as defined by RECIST version (v)1.1. Previously irradiated lesions can be counted as target lesions if clearly progressing after radiation
• Patients may have asymptomatic central nervous system (CNS) metastases or treated CNS metastases if they are not currently receiving corticosteroids greater than dexamethasone 2 mg daily or equivalent for 7 days prior to the first dose of study drug. Patients should have completed stereotactic radiation or whole-brain radiation at least 2 weeks prior to cycle 1, day 1
• Anticonvulsants at a stable dose are allowed
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly). Birth control pills on their own do not achieve that rate * Women of childbearing potential must have a negative pregnancy test (serum or urine) within 72 hours of the start of study drug administration * Women who have recently given birth must no longer be breastfeeding * Women childbearing potential must agree to follow instructions for methods of contraception for time of the study. Women of childbearing potential should use adequate methods to avoid pregnancy for 5 months after the last dose of investigational drug * Males who are sexually active with women of childbearing potential must agree to follow instructions for methods of contraception and continue to use contraception for 7 months after last does of investigational drug

Exclusion Criteria

• Patients with an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires systemic steroids greater than dexamethasone 2 mg daily (or equivalent) or immunosuppressive agents within the past 3 months will be ineligible. Patients with a documented history of severe autoimmune disease but have been off of steroids and immunosuppressive agentsfor greater than 3 months, or only require intermittent steroid bursts may be eligible following discussion and approval from the principal investigator (PI). Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of inhaled steroids or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement, or psoriasis not requiring systemic therapy (within the past 3 years) or type 1 diabetes on stable insulin will not be excluded from the study
• Treatment with systemic immunosuppressive medications including but not limited to, dexamethasone at doses > 2 mg or equivalent dose of other corticosteroids, cyclophosphamide, tacrolimus, sirolimus, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor (anti-TNF) agents within 2 weeks prior to initiation of trial therapy. Inhaled or topically applied steroids, and acute and chronic standard-dose NSAIDs are permitted. Replacement steroids are also permitted. Steroids required as prophylaxis for contrast allergies to scans are permitted
• Active systemic infection requiring systemic antibiotic treatment within 72 hours prior to first dose of study treatment
• Prior treatment with anti-CTLA4 antibodies. Prior anti-PD1 or anti-PDL1 therapy is allowed
• Untreated symptomatic CNS metastases. Patients with asymptomatic CNS metastases are eligible. Patient with treated symptomatic brain metastases are eligible provided they meet all of the following criteria: *Completed stereotactic radiosurgery or whole- brain radiation at least 2 weeks prior to cycle 1, day 1 * No evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy * Ongoing steroid requirement for CNS =< 2 mg of dexamethasone per day (or equivalent) as therapy for CNS disease; anticonvulsants at a stable dose are allowed
• History of leptomeningeal carcinomatosis
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Subjects must not have received vaccines containing live virus for prevention of infectious diseases within 12 weeks prior to the first dose of study drug. * The use of inactivated seasonal influenza vaccines (e.g., Fluzone) will be permitted on study without restriction
• Any approved systemic anti-cancer therapy, within 3 weeks prior to initiation of study treatment
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 21 days prior to enrollment
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Major surgery or traumatic injury within 4 weeks of starting study drug
• Women who are pregnant or lactating
• Any underlying medical condition that in the treating investigator’s opinion will make the administration of study drug hazardous to the patient or would obscure the interpretation of adverse events
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients with prior exposure to hepatitis, but no evidence of active or chronic infection, may be eligible
• Absolute neutrophil count (ANC) < 1,000 cells/uL (without granulocyte colony-stimulating factor support within 2 weeks prior to cycle 1, day 1) (obtained within 14 days prior to the first study treatment)
• Platelet count < 75,000/uL (without transfusion within 2 weeks prior to cycle 1, day 1) (obtained within 14 days prior to the first study treatment)
• Hemoglobin < 8.0 g/dL (Patients may be transfused to meet this criterion) (obtained within 14 days prior to the first study treatment)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >= 2.5 x upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and/or ALT >= 5 x ULN (obtained within 14 days prior to the first study treatment)
• Serum bilirubin >= 1.5 x ULN (Patients with known Gilbert disease who have serum bilirubin level >= 3 x ULN may be enrolled) (obtained within 14 days prior to the first study treatment)
• Institutional normalized ratio (INR) and partial thromboplastin time (aPTT) >= 1.5 x ULN (This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose) (obtained within 14 days prior to the first study treatment)