Ibrutinib and Nivolumab in Treating Participants With Metastatic Solid Tumors

PRIMARY OBJECTIVES:

I. Evaluate the effect of the ibrutinib therapy on circulating levels of myeloid derived suppressor cells MDSC.

SECONDARY OBJECTIVES:

I. Assess safety of the study combination in study subjects.

EXPLORATORY OBJECTIVES:

I. Evaluate the effect of the ibrutinib/nivolumab therapy on circulating levels of MDSC.

II. Evaluate the effect of the ibrutinib and ibrutinib/nivolumab therapy on the immunosuppressive function of circulating MDSC by measuring their ability to inhibit T cell proliferation and natural killer cell mediated antibody dependent cell cytotoxicity.

III. Study the effect of ibrutinib and ibrutinib/nivolumab therapy on levels of circulating innate and adaptive immune cells such as natural killer cell and T lymphocyte subsets.

IV. Study circulating MDSC levels at the time of disease progression. V. Evaluate in a preliminary fashion the effect of the regimen on progression-free survival.

OUTLINE:

Participants receive ibrutinib orally (PO) daily for 15 days. After 7 days receiving ibrutinib, participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and 15. Courses with nivolumab repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, participants are followed up every 3 months.

Inclusion criteria

• Patients with biopsy-proven metastatic solid tumor and be eligible to receive nivolumab per standard of care
• Patients will be allowed to have any number of prior lines of therapy for metastatic cancer
• Patients with measurable and non-measurable disease are allowed to participate
• Absolute neutrophil count (ANC) ? 1.5 x 10^3/mm^3
• Hemoglobin (Hgb) ? 9 g/dL
• Platelet count ? 100 x10^3/mm^3
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ? 2.5 x upper limit of normal (ULN) or ? 5 x ULN in patients with liver metastases
• Prothrombin time ? 1.5 x ULN
• Total bilirubin ? 1.5 x ULN (unconjugated bilirubin of < 3 x ULN for patients with known Gilbert syndrome)
• Creatinine clearance of ? 50 ml/min by Cockcroft-Gault equation
• Corrected QT interval of < 480 msec (using either Bazett?s or Fridericia's formula)
• Life expectancy of > 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status 0 ? 2
• Sexually active women with child bearing potential must have a negative pregnancy test obtained within 14 days prior to initiating study treatment
• Sexually active 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 after completion of study treatment administration; adequate contraception includes methods such as oral contraceptives, double barrier method (condom plus spermicide or diaphragm), or abstaining from sexual intercourse

Exclusion criteria

• History of prior therapy with ibrutinib or nivolumab
• Unable to swallow capsules or having disease that is significantly affecting gastrointestinal function and/or inhibiting small intestine absorption
• Diagnosis of congenital or acquired immunodeficiency with the exception of chemotherapy induced immune suppression
• Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids of greater than or equal to prednisone 10 mg/day or other immunosuppressive agents; patients with history of adequately treated Hashimoto?s thyroiditis will be eligible; patients requiring a short course of a high dose prednisone burst to treat asthma or common obstructive pulmonary disease will also be eligible 5 days following completion of the prednisone treatment
• Use of systemic steroids at a dose above 10 mg/day of prednisone or prednisone equivalent in cycle 1 of study therapy; systemic steroids must be discontinued at least 5 days prior to initiating study therapy; exception will be given to patients who develop immune related adverse events that necessitate use of steroids or other immune suppressive agents; following cycle 1 of study treatment, the use of systemic steroids will be allowed per discretion of the treating physician
• Active, non-infectious pneumonitis
• Ongoing or active infection requiring systemic therapy
• History of being positive for human immunodeficiency virus (HIV)
• History of hepatitis B or C
• History of receiving live vaccine within 30 days of planned start of study therapy
• Central nervous system (CNS) metastases or leptomeningeal carcinomatosis; patients with history of adequately treated brain metastases that are stable for > 2 weeks prior to the first dose of study regimen are eligible as long they no longer require steroids and have no seizures or worsening focal neurologic symptoms; anti-epileptic therapy will be allowed
• Patients who had prior systemic chemotherapy within 3 weeks (or < 5 half-lives ? whichever is longer)
• Prior radiation therapy within 2 weeks of study enrollment
• Prior investigational therapy within 4 weeks
• Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose of study drug; port placement will not be considered major or minor surgery
• Any inter-current, uncontrolled systemic illness or any medical or psychiatric condition that in the opinion of the investigator would make the study therapy unsafe to the patient
• Unable to understand and sign informed consent form
• Uncontrolled, active cardiovascular disease including, but not limited to: symptomatic congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification, unstable angina pectoris, cardiac arrhythmia
• Any medications or substances that are strong inhibitors or inducers of CYP 3A4 need to be discontinued prior to initiation the study therapy and for the duration of ibrutinib treatment; patients can resume these medications 3 days after completion of ibrutinib course
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as ibrutinib or nivolumab