TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas
Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With BMS-986178 and Local Radiation in Low-Grade B-Cell Lymphomas
4 other identifiers
interventional
14
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 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. Anti-OX40 antibody is a monoclonal antibody that enhances the activation of T cells, immune cells that are important for fighting tumors Radiation therapy uses high energy x-rays to kill cancer cells and may make them more easily detected by the immune system. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Apr 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 19, 2018
CompletedFirst Posted
Study publicly available on registry
January 25, 2018
CompletedStudy Start
First participant enrolled
April 9, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 9, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 10, 2024
CompletedDecember 11, 2024
December 1, 2024
6.5 years
January 19, 2018
December 6, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Number of participants experiencing Dose-limiting Toxicities (DLT) within 8 weeks of treatment initiation
Dose-limiting toxicities (DLTs) as assessed as the following hematologic toxicities (grades per CTCAE) in all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178 (not including events due to disease progression or definitively unrelated to study drugs): * Febrile neutropenia * Thrombocytopenia Grade 4 or Grade 3 with bleeding or platelet transfusion * Anemia Grade 4 * Non-hematological toxicity ≥ grade 3, except: * Alopecia controlled by medical management * Nausea controlled by medical management * Grade 3 or 4 electrolyte abnormalities not associated with adverse events, persist \< 72 hours, and either spontaneously resolve or respond to intervention. * Grade 3 or 4 elevation of amylase or lipase not associated with pancreatitis * Grade 3 endocrinopathy * Grade 3 infusion reaction returning to ≤ Grade 1 in \< 6 hours * Grade 3 skin rash not requiring systemic steroid or other immunosuppressive therapy
Up to 8 weeks
Secondary Outcomes (2)
Overall Response Rate (ORR)
Up to 96 weeks
Progression-Free Survival (PFS)
up to 96 weeks
Study Arms (1)
Treatment (radiation therapy, SD-101, BMS-986178)
EXPERIMENTALPatients 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.
Interventions
Given IV, intratumoral
Correlative studies
Undergo radiation therapy
Given intratumorally
Eligibility Criteria
You may qualify if:
- 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
- +1 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ronald Levylead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Stanford University, School of Medicine
Palo Alto, California, 94304, United States
Related Publications (2)
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.
PMID: 35135810DERIVEDMooney 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.
PMID: 34780125DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ronald Levy
Stanford University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Robert K. and Helen K. Summy Professor
Study Record Dates
First Submitted
January 19, 2018
First Posted
January 25, 2018
Study Start
April 9, 2018
Primary Completion
October 9, 2024
Study Completion
October 10, 2024
Last Updated
December 11, 2024
Record last verified: 2024-12
Data Sharing
- IPD Sharing
- Will not share