Study of SD-101 in Combination With Localized Low-dose Radiation in Patients With Untreated Low-grade B-cell Lymphoma

Inclusion Criteria: * Biopsy confirmed, untreated, low-grade B-cell lymphoma, including follicular (Grade 1, 2, or 3A) \[Harris, Swerdlow et al. 2008\] or marginal, or CLL/SLL with lymph node involvement. * At least 2 sites of measurable disease per Cheson criteria (must measure at least 1.5 cm in any diameter or 1.0 cm in the shortest diameter if one of the diameters is not ≥ 1.5 cm), one of which must be palpable and easily accessible in a low-risk site (eg, inguinal, axillary, cervical, subcutaneous) for intratumoral injection (denoted as "Lesion A" in Treatment Cycle 1) and at least one additional untreated lesion that is located outside the radiation field of the treated lesion (Lesion A) and is accessible for an FNA aspirate. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 * Aged 18 years and older * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelet count \> 100,000/µL * Serum creatinine (Cr) ≤ 1.5 x upper limit of normal (ULN). * Serum total bilirubin ≤ 1.5 x the ULN. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * International normalized ratio or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy and the PT or partial thromboplastin time (PTT) must be within the therapeutic range of the intended use of anticoagulants. * Activated PTT (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy, and the PT or PTT is within therapeutic range of intended use of anticoagulants. * Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to taking study medication if of childbearing potential as defined in this protocol. Women of childbearing potential (WOCBP) must be willing to use 2 medically acceptable method of contraceptive from Day 1 through 120 days after the last dose of trial treatment. The 2 medically acceptable birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), cooper intrauterine device, sponge, or spermicide as per local regulations or guidelines. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents). * Ability to understand and sign informed consent form (ICF) and comply with treatment protocol Exclusion Criteria: * Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy (including immune modulators or systemic corticosteroids) within 7 days prior to study enrollment. * Positive for hepatitis B (HBsAg reactive), HCV ribonucleic acid (RNA) qualitative, or human immunodeficiency virus (HIV)( HIV 1/2 antibodies) * Diagnosis of mantle or diffuse large-cell lymphoma, Grade 3B follicular lymphoma \[Harris, Swerdlow et al. 2008\] or gastric mucosa-associated lymphoid tissue (MALT) lymphoma * Clinically significant pleural effusion * Active infection including cytomegalovirus * Pregnant or breast feeding within the projected duration of trial participation through 4 months after the last dose of study treatment. * Autoimmune disease including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjӧgren's syndrome, autoimmune thrombocytopenia, history of uveitis, or other if clinically significant * Lymphoma involvement of the central nervous system * Received any prior therapy for lymphoma * Use of any investigational agent within the last 28 days * Serious, non-healing wound, ulcer, or bone fracture. * If a subject received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to enrollment. * Clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication within 1 year prior to Day -1 (Visit 1); Grade II or greater peripheral vascular disease at study entry * Any other significant medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study * History of sensitivity to any component of SD-101 * A diagnosis of cancer within the last 3 years prior to enrollment or any known additional malignancy that is progressing or requires active treatment. Exceptions are B-cell lymphoma, basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer. * Is taking systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication