TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas

Inclusion Criteria:

   - Biopsy confirmed low-grade B-cell lymphoma, excluding gastric MALT lymphoma, high-risk
   mantle cell lymphoma, and currently transformed lymphoma

   - Patients must have at least one site of disease (cervical, axillary, inguinal, or
   subcutaneous) that is accessible for intratumoral injection of SD-101 (diameter ≥10mm)
   percutaneously and presents a low risk for complications from direct injections.

   - Patients must have at least one site of measurable disease, other than the injection
   site, which is not included in the radiation field

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

   - Absolute neutrophil count (ANC) >= 1000/mm^3 independent of growth factor support

   - Platelets: >= 100,000/mm^3 or >= 50,000/mm^3 if known or suspected bone marrow
   involvement, independent of transfusion support in either situation

   - Hemoglobin: >= 8 g/dL (may be transfused)

   - Creatinine: Creatinine clearance > 25 ml/min

   - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 3 x upper limit of
   normal (ULN)

   - Bilirubin: =< 1.5 x ULN (except for subjects with Gilbert's Syndrome or of non-hepatic
   cause)

   - Must be at least 4 weeks since treatment with standard or investigational
   chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, any monoclonal
   antibodies or immunotherapy, and recovered from any clinically significant toxicity
   experienced during treatment

   - Women of childbearing potential and men who are sexually active must be practicing a
   highly effective method of birth control during and after the study consistent with
   local regulations regarding the use of birth control methods for subjects
   participating in clinical trials; men must agree to not donate sperm during and after
   the study; for sexually active women of childbearing potential, these restrictions
   apply for 5 months after the last dose of study drug; for sexually active men, these
   restrictions apply for 7 months after the last dose of study drug

   - Women of childbearing potential must have a negative serum (beta-human chorionic
   gonadotropin [beta-hCG]) or urine pregnancy test at screening, within 24 hours of the
   first dose of anti-OX40 antibody, and every four weeks while on study treatment; women
   who are pregnant or breastfeeding are ineligible for this study

   - Life expectancy greater than 3 months

   - Ability to comply with the treatment schedule

   - Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

   - Currently transformed lymphoma, high-risk mantle cell lymphoma, or gastric MALT
   lymphoma.

   - Need for immediate treatment or cytoreduction.

   - No easily accessible site for direct percutaneous injection with low-risk for
   potential complications.

   - Autoimmune disease requiring treatment within the last 5 years including systemic
   lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome,
   autoimmune thrombocytopenia, uveitis, or other if clinically significant

   - Major surgery within 4 weeks of enrollment, or a wound that has not fully healed

   - Vaccinated with live, attenuated vaccines within 4 weeks of enrollment

   - Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or
   active hepatitis B virus infection or any uncontrolled active systemic infection

   - Known central nervous system (CNS) lymphoma

   - Patients with a history of prior malignancy with the exception of non-melanoma skin
   cancer, stage 1 prostate cancer that does not require treatment, or other malignancy
   that has undergone potentially curative therapy with no evidence of disease for the
   last 2 years and that is deemed by the investigators to be at low risk for recurrence.
   In situ cancer of any type and noninvasive follicular thyroid neoplasm with
   papillary-like nuclear features (NIFTP) is not an exclusion, though if surgery or
   other definitive intervention is planned, it should be completed prior to enrollment.

   - History of significant allergic reactions attributed to compounds of similar
   composition to SD-101 or BMS-986178

   - Treatment with an immunosuppressive regimen of corticosteroids or other
   immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study
   treatment; Note: patients may take up to 5 mg of prednisone or equivalent daily;
   topical and inhaled corticosteroids in standard doses are allowed

   - Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3
   congestive heart failure; myocardial infarction within the past 6 months; unstable
   angina; coronary angioplasty with the past 6 months; uncontrolled atrial or
   ventricular cardiac arrhythmias)

   - Pregnant or breast feeding

   - Any other medical history, including laboratory results, deemed by the investigator
   likely to interfere with their participation in the study, or to interfere with the
   interpretation of the results