This phase I trial studies the side effects of intratumoral injection of SD-101 and BMS-986178 in treating patients with solid malignancies that have spread to other places in the body. The TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. BMS-986178 is a monoclonal anti-OX40 antibody that enhances the activation of T cells, immune cells that are important for fighting tumors. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS-986178 may work better in treating patients with advanced solid tumors.
PRIMARY OBJECTIVES: I. To determine the safety and tolerability of intratumoral TLR9 agonist SD-101 (SD-101) in combination with intratumoral and intravenous anti-OX40 antibody BMS 986178 (BMS-986178) in patients with advanced solid tumors. SECONDARY OBJECTIVES: 1. To evaluate the efficacy of treatment with intratumoral SD 101 in combination with intratumoral and intravenous BMS 986178 in patients with advanced solid tumors. 2. To evaluate changes in pharmacodynamic endpoints in serial tumor biopsies from I TUMOR treated and untreated sites of disease. OUTLINE: SAFETY COHORT: Patients receive TLR9 agonist SD-101 intratumorally (IT) on days 1, 8 and 15. Patients also receive anti-OX40 antibody BMS 986178 IT on days 8 and 15, and intravenously (IV) over 30 minutes on days 8, 29 and 58. EXPANSION COHORT: Patients receive TLR9 agonist SD-101 IT on days 1, 8 and 15. Patients also receive anti-OX40 antibody BMS 986178 IT on days 1, 8 and 15, and IV over 30 minutes on days 1, 29 and 58. After completion of study treatment, patients are followed up every 3-6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Given IT or IV
Given IT
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Incidence of adverse events of intratumoral injections of study drugs
This outcome will be measured for any participant who has received at least one dose of any study medication. Treatment-limiting toxicities will be assessed using CTCAE v5.0. All adverse events will be recorded. Treatment-limiting toxicities are defined as; * Hematologic toxicities: Febrile neutropenia; Grade 3 \&4 thrombocytopenia; Grade 4 anemia unexplained with exception that toxicities can clearly be determined due to disease progression and/or unrelated to SD-101 or BMS-986178. * Non-hematological toxicity ≥ Grade 3; Alopecia; Nausea; Grade 3 or 4 electrolyte abnormalities; Grade 3 or 4 elevation of amylase or lipase not associated with pancreatitis; Grade 3 endocrinopathy controlled by hormone replacement; Grade 3 infusion reaction that returns to Grade 1 in \< 6 hours; Grade 3 skin rash not requiring systemic steroid therapy or other systemic immunosuppressive therapy. * Doses should be delayed if any Grade ≥ 2 toxicities are not resolved to Grade ≤ 1 or baseline by next cycle.
Time frame: Up to week 96
Overall response rate
Tumor response assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions, and assessed by physical measurement; computed tomography (CT), positron emission tomography (PET)-CT. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria
Time frame: Up to 3 years
Progression-Free survival (PFS)
Progression-Free Survival is defined as the time elapsed between treatment initiation (Day 1) and tumor progression or death from any cause. Progression will be defined using RECIST v1.1.
Time frame: Up to 3 years
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