A Phase I/II Study of Intratumoral Injection of SD-101

Inclusion Criteria

• Biopsy-confirmed low-grade B-cell lymphoma, specifically, follicular grade 1 or 2, or 3A marginal zone or small lymphocytic lymphoma; patients must have relapsed from or are refractory to prior therapy
• Patients must have at least one site of disease that is accessible for intratumoral injection of SD-101 and of ipilimumab (diameter ≥ 10mm), percutaneously
• Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the study
• Patients must have measurable disease other than the injection site or biopsy site
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 [corresponds to Karnofsky Performance Status (KPS) of ≥ 70]
• White blood cell count (WBC) ≥ 2000/µL (2 x 10^9/L)
• Absolute neutrophil count (ANC) ≥ 1000/µL (0.5 x 10^9/L)
• Platelets ≥ 75 x 10^3/µL (75 x 10^9/L)
• Hemoglobin ≥ 8 g/dL (may be transfused)
• Creatinine ≤ 2.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN for subjects without liver metastasis; ≤ 5 times for liver metastases
• Bilirubin ≤ 2.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
• No active or chronic infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
• Must be at least 4 weeks since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, and 8 weeks since any monoclonal antibodies or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
• Patients of reproductive potential must agree to use an effective (> 90% reliability) form of contraception during the study and for 6 months following the last study drug administration
• Women of reproductive potential must have negative urine pregnancy test
• Life expectancy greater than 4 months
• Able to comply with the treatment schedule
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Pre-existing autoimmune or antibody mediated disease including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, Addison's disease, but excluding the presence of auto-antibodies without clinical autoimmune disease
• History of inflammatory bowel disease (eg, Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis of any origin
• Any history of diverticulitis, or evidence of diverticulitis at baseline, including evidence limited to computed tomography (CT) scan only (note diverticulosis is not an exclusion criterion)
• Severe psoriasis
• Active thyroiditis
• History of uveitis
• Known history of HIV; patients with Acquired Immunodeficiency Syndrome (AIDS) are excluded
• Patients with active infection or with a fever > 38.5 degrees C within 3 days prior to the first scheduled treatment
• Central nervous system (CNS) lymphoma
• Prior malignancy (active within 5 years of screening) except basal cell or completely excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell carcinoma of the cervix
• History of allergic reactions attributed to compounds of similar composition to SD-101 or ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] antibodies)
• Current anticoagulant therapy (EXCEPTION acetylsalicylic acid ≤ 325 mg per day allowed)
• Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (eg, methotrexate, rapamycin) within 30 days of study treatment; note patients with adrenal insufficiency may take up to 5 mg of prednisone or equivalent daily; topical and inhaled corticosteroids in standard doses are allowed
• Significant cardiovascular disease [ie, New York Heart Association (NYHA) class 3 con