TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas
NCT ID: NCT03410901
Last Updated: 2024-12-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
14 participants
INTERVENTIONAL
2018-04-09
2024-10-10
Brief Summary
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Detailed Description
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I. To determine the safety and tolerability of TLR9 agonist SD-101 (SD-101) in combination with anti-OX40 antibody BMS 986178 (BMS-986178) and local low-dose radiation in patients with low-grade B-cell lymphoma. Adverse events and grades to be assessed by Common Terminology Criteria for Adverse Events (CTCAE) II. To determine the recommended phase 2 dose (RP2D) of BMS-986178 in combination with intratumoral SD-101 and radiation in patients with low-grade B-cell lymphoma.
SECONDARY OBJECTIVES:
I. To evaluate preliminary efficacy by assessing overall response rate and progression-free survival after treatment with intratumoral SD-101 in combination with BMS-986178 and radiation in patients with low-grade B-cell lymphoma.
OUTLINE: This is a phase I study of the combination of TLR9 agonist SD-101, anti-OX40 antibody BMS 986178, and local low-dose radiation therapy.
Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 intravenously (IV) on days 3, 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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (radiation therapy, SD-101, BMS-986178)
Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 and anti-OX40 antibody BMS-986178 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 IV on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
Anti-OX40 Antibody BMS 986178
Given IV, intratumoral
Laboratory Biomarker Analysis
Correlative studies
Radiation Therapy
Undergo radiation therapy
TLR9 Agonist SD-101
Given intratumorally
Interventions
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Anti-OX40 Antibody BMS 986178
Given IV, intratumoral
Laboratory Biomarker Analysis
Correlative studies
Radiation Therapy
Undergo radiation therapy
TLR9 Agonist SD-101
Given intratumorally
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Ronald Levy
OTHER
Responsible Party
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Ronald Levy
Robert K. and Helen K. Summy Professor
Principal Investigators
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Ronald Levy
Role: PRINCIPAL_INVESTIGATOR
Stanford University
Locations
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Stanford University, School of Medicine
Palo Alto, California, United States
Countries
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References
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Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382.
Mooney KL, Czerwinski DK, Shree T, Frank MJ, Haebe S, Martin BA, Testa S, Levy R, Long SR. Serial FNA allows direct sampling of malignant and infiltrating immune cells in patients with B-cell lymphoma receiving immunotherapy. Cancer Cytopathol. 2022 Mar;130(3):231-237. doi: 10.1002/cncy.22531. Epub 2021 Nov 15.
Other Identifiers
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NCI-2017-02452
Identifier Type: REGISTRY
Identifier Source: secondary_id
LYMNHL0144
Identifier Type: OTHER
Identifier Source: secondary_id
IRB-44250
Identifier Type: -
Identifier Source: org_study_id