This phase I/II trial studies the side effects and best dose of anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) agonistic monoclonal antibody BMS-986156 (BMS-986156) when given together with ipilimumab and nivolumab with or without stereotactic body radiation therapy and to see how well they work in treating patients with lung/chest or liver cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as BMS-986156, ipilimumab, and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. It is not yet known whether giving BMS-986156, ipilimumab, and nivolumab with or without stereotactic body radiation therapy will work better in treating patients with lung/chest or liver cancers.
PRIMARY OBJECTIVES: I. To determine the safe dose of BMS-986156 and dose limiting toxicities (DLT) (30 mg versus \[vs\] 100 mg) when combined with ipilimumab (3 mg/kg) for patients with metastatic cancer. II. To evaluate the safety and toxicity profile of ipilimumab (3mg/kg) with BMS-986156 (30 or 100 mg) administered in combination with stereotactic body radiation therapy (SBRT) targeting 1-4 LIVER lesion(s) for patients with metastatic cancers. III. To evaluate the safety and toxicity profile of ipilimumab (3mg/kg) with BMS-986156 (30 or 100 mg) administered in combination with SBRT targeting 1-4 LUNG lesion(s) for patients with metastatic cancer. IV. To determine safety and toxicity profile of nivolumab (480 mg) with BMS-986156 (30 mg) administered in combination with SBRT targeting 1-4 LIVER lesion(s) for patients with metastatic cancers. V. To determine safety and toxicity profile of nivolumab (480 mg) with BMS-986156 (30 mg) administered in combination with SBRT targeting 1-4 LUNG lesion(s) for patients with metastatic cancers. SECONDARY OBJECTIVES: I. To determine antitumor activity of ipilimumab therapy with BMS-986156 (30 or 100 mg) as well as nivolumab with BMS-986156 (30 mg) with SBRT treatment for 1-4 lung lesions in both the SBRT treated lesion and non-irradiate tumors. II. To determine antitumor activity of ipilimumab therapy with or without BMS-986156 (30 or 100 mg) as well as nivolumab with BMS-986156 (30 mg) with SBRT treatment for 1-4 liver lesions in both the SBRT treated lesion and non-irradiate tumors. III. To compare response and progression of the non-irradiated tumors between BMS-986156 with ipilimumab vs BMS-986156 with nivolumab, using both immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.1. IV. To evaluate the predictive potential value of tumor-associated and systemic immune biomarkers for therapy effectiveness and toxicity prediction. V. To evaluate whether skeletal mass, neutrophil, neutrophil to lymphocyte ratio, and tumor bulk are correlated with clinical outcomes and adverse events. VI. To evaluate whether tumor kinetics in combination with clinical correlates can help determine treatment response. VII. To evaluate whether tumor mutational burden correlates with improved clinical outcomes and response criteria. OUTLINE: This is a phase I, dose-escalation study of anti-GITR agonistic monoclonal antibody BMS-986156, followed by a phase II study. Patients are assigned to 1 of 3 groups. GROUP I: Patients receive ipilimumab intravenously (IV) over 90 minutes and anti-GITR agonistic monoclonal antibody BMS-986156 IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 1 of cycle 5 (day 85), patients receive nivolumab IV over 30 minutes. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. GROUP II: Patients receive ipilimumab IV over 90 minutes and anti-GITR agonistic monoclonal antibody BMS-986156 IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 2, patients then undergo SBRT on days 29-32 for 4 fractions or on days 29-40 for 10 fractions. Beginning day 1 of cycle 5 (day 85), patents receive nivolumab IV over 30 minutes. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. GROUP III: Patients receive nivolumab IV over 30 minutes and anti-GITR agonistic monoclonal antibody BMS-986156 over 60 minutes on day 1. Patients also undergo SBRT over 30-45 minutes on days 1-4 for 4 fractions or on days 1-12 for 10 fractions. Treatment repeats every 28 days for up to 26 cycles of nivolumab and for up to 4 cycles of anti-GITR agonistic monoclonal antibody BMS-986156 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 2-4 months for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Given IV
Given IV
Undergo SBRT
M D Anderson Cancer Center
Houston, Texas, United States
Number of Dose Limiting Toxicities (DLTs)
Evaluate dose of BMS-986156 (30 mg vs 100 mg) and dose limiting toxicities (DLTs) when combined with ipilimumab (3 mg/kg), and evaluate DLTs when BMS-986156 administered in combination with ipilimumab (3 mg/kg) or nivolumab (480 mg) with SABR
Time frame: Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0)
Assess SBRT and Palliative Radiation Completion
Explore antitumor activity with SBRT and palliative radiation.
Time frame: Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0)
Immune-related Tumor Response
Number of immune related responses of different immunotherapy schemes with or without SABR; Assessing complete response (CR), partial response (PR), and stable disease (SD)
Time frame: Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0)
Out-of-field (Abscopal) Disease Control Rate (ACR)
Patient's change of tumor since intiation of treatment and patient's exhibiting out of field disease control.
Time frame: Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0)
Out-of-field (Abscopal) Response Rate (ARR)
Assesses partial response (PR) rate and complete response (CR) rate
Time frame: Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0)
Tumor Burden: Disease Control Rate
Assessing complete response (CR), partial response (PR), and stable disease (SD)
Time frame: Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0)
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