TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients with Low-Grade B-Cell Non-Hodgkin Lymphomas
This phase I trial studies the side effects and best dose of TLR9 agonist SD-101 when given together with anti-OX40 antibody BMS 986178 and radiation therapy in treating patients with low-grade B-cell non-Hodgkin lymphomas. TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. Immunotherapy with monoclonal antibodies, such as anti-OX40 antibody BMS 986178, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill cancer cells. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS 986178 and radiation therapy may work better in treating patients with low-grade B-cell non-Hodgkin lymphomas.
- Biopsy-confirmed low-grade B-cell lymphoma, including grade 1, 2, or 3A follicular lymphoma, marginal zone lymphoma (excluding gastric MALT lymphoma), small lymphocytic lymphoma, lymphoplasmacytic lymphoma, or indolent mantle cell lymphoma that is not high-risk by Mantle Cell Lymphoma International Prognostic Index (MIPI or MIPI); patients may be newly diagnosed or previously treated
- Patients must have at least one site of disease that is accessible for intratumoral injection of SD-101 (diameter >= 10 mm), percutaneously; this should be a cervical, axillary, inguinal, femoral, or subcutaneous site that is considered at low risk for complications from direct injection
- 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 with hyperbilirubinemia 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 within the 24 hours prior to each intravenous dose of anti-OX40 antibody; 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
- Patients currently with transformed lymphoma, mantle cell lymphoma who have high-risk Mantle Cell Lymphoma International Prognostic Index (MIPI or Mantle Cell Lymphoma International Prognostic Index Combined Biologic Index [MIPIb]) score or gastric mucosa-associated lymphoid tissue (MALT) lymphoma
- Patients who require immediate treatment or cytoreduction, as deemed by their physician or the study investigators
- Patients who do not have an easily accessible tumor site (cervical, axillary, inguinal/femoral, or subcutaneous) or whose accessible sites all present a high risk for potential complications from direct injections
- Autoimmune disease requiring treatment within the last 2 years including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, autoimmune thrombocytopenia, uveitis, or other if clinically significant; patients with endocrinopathies on adequate replacement therapy, type I diabetes, or vitiligo are not excluded; resolved childhood autoimmune diseases/syndromes or those that occurred due to an external trigger (e.g., post-streptococcal glomerulonpephritis) are also not excluded
- 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, carcinoma in situ of the cervix, in situ carcinoma of the bladder, 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
- 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, inhaled and intraarticular 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
Locations & Contacts
Status: Temporarily closed to accrual
Contact: Ronald Levy
Trial Objectives and Outline
I. To determine the safety and tolerability of TLR9 agonist SD-101 (SD-101) in combination with intratumoral and intravenous anti-OX40 antibody BMS 986178 (BMS-986178) and local low-dose radiation in patients with low-grade B-cell lymphoma.
II. To determine the recommended phase 2 dose (RP2D) of intravenous BMS-986178 in combination with intratumoral BMS-986178, intratumoral SD-101 and radiation in patients with low-grade B-cell lymphoma.
I. To evaluate preliminary efficacy by assessing overall response rate and progression-free survival after treatment with intratumoral SD-101 in combination with intratumoral and intravenous BMS-986178 and local low-dose radiation in patients with low-grade B-cell lymphoma.
Patients undergo radiation therapy on days 1-2. Patients also receive TLR9 agonist SD-101 intratumorally (IT) and anti-OX40 antibody BMS-986178 IT on days 2, 9, 16, 23, and 30 and BMS-986178 intravenously (IV) on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 72 weeks.
Trial Phase & Type
Stanford Cancer Institute Palo Alto
Secondary IDs NCI-2017-02452
Clinicaltrials.gov ID NCT03410901