BMS-986156, Ipilimumab, and Nivolumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Lung/Chest or Liver Cancers

Advanced Malignant Solid Neoplasm, Metastatic Carcinoma in the Liver, Metastatic Carcinoma in the Lung, Metastatic Malignant Neoplasm in the Thoracic Cavity, Metastatic Malignant Solid Neoplasm

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.

United States

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