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.
PRIMARY OBJECTIVES: 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Given IV, intratumoral
Correlative studies
Undergo radiation therapy
Given intratumorally
Stanford University, School of Medicine
Palo Alto, California, United States
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
Time frame: Up to 8 weeks
Overall Response Rate (ORR)
Overall Response Rate (ORR), assessed as the sum of the complete response (CR) and partial response (PR) rates, as determined by computed tomography (CT) or positron emission tomography (PET)/CT and evaluated per the Lugano classification for low-grade B-cell lymphomas, in all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178. Lugano classification: * CR: No detectable disease by CT or PET/CT scan * PR: ≥ 50% decrease in size of target lesions * No response (NR) / Stable disease (SD): \< 50% decrease in size of target lesions * Progressive disease (PD): Target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 cm or +50%. Reported for 24, 48, 72 and 96 weeks.
Time frame: Up to 96 weeks
Progression-Free Survival (PFS)
Progression-free survival (PFS) as determined for all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178, from start of treatment to disease progression per the Lugano classification or death from any cause, through 96 weeks. Progression assessed per the Lugano classification. Patients who were last known to be alive and progression-free will be censored at the latest disease assessment. Lugano classification: * CR: No detectable disease by CT or PET/CT scan * PR: ≥ 50% decrease in size of target lesions * No response (NR) / Stable disease (SD): \< 50% decrease in size of target lesions * Progressive disease (PD): Target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 cm or +50%. Reported for 24, 48, 72 and 96 weeks.
Time frame: up to 96 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.