A Phase 1/2 interventional study of Anti-GITR Agonistic Monoclonal Antibody BMS-986156 and Ipilimumab in Advanced Malignant Solid Neoplasm, Metastatic Carcinoma in the Liver and Metastatic Carcinoma in the Lung, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-03.
Sponsored by M.D. Anderson Cancer Center · Phase 1/2, Interventional, and Treatment
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.
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Exclusion Criteria:
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. 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.
Drug: Anti-GITR Agonistic Monoclonal Antibody BMS-986156 · Biological: Ipilimumab · Biological: Nivolumab
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.
Drug: Anti-GITR Agonistic Monoclonal Antibody BMS-986156 · Biological: Ipilimumab · Biological: Nivolumab · Radiation: Stereotactic Body Radiation Therapy
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.
Drug: Anti-GITR Agonistic Monoclonal Antibody BMS-986156 · Biological: Nivolumab · Radiation: Stereotactic Body Radiation Therapy
Given IV
Also known as: Anti-GITR MoAb BMS-986156, BMS 986156, BMS-986156, GITR Agonist BMS-986156, TNFRSF18 Agonist BMS-986156
Given IV
Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy
Given IV
Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo
Undergo SBRT
Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy
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)
Dates of recruitment period: 08/2019 to 12/2021; Location: Single center trial that recruited patients at one hospital site (MD Anderson Cancer Center, Houston, TX)
| Milestone | Ipilimumab + BMS-986156 (30 mg/kg) Arm | Ipilimumab + BMS-986156 (100 mg/kg) Arm | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Started | 10 | 10 | 10 | 20 |
| Completed | 0 | 0 | 0 | 1 |
| Not completed | 10 | 10 | 10 | 19 |
| Withdrew: Adverse event | 3 | 1 | 1 | 0 |
| Withdrew: Death | 2 | 3 | 1 | 3 |
| Withdrew: Withdrawal by subject | 1 | 1 | 1 | 6 |
| Withdrew: Discontinued due to disease progression | 4 | 5 | 7 | 10 |
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
| Dose limiting toxicities | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Number of Dose Limiting Toxicities (DLTs) | 1 | 1 | 0 | 0 |
Explore antitumor activity with SBRT and palliative radiation.
| Count of participants | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Completion of SBRT without interruption due to RT-related AEs | — | — | 10 | 20 |
| Re-induction of SBRT due to progression per protocol | — | — | 0 | 4 |
| Received palliative RT while receiving immunotherapy | — | — | 0 | 3 |
| Received palliative RT after finishing all protocol-specified therapy | — | — | 2 | 5 |
Number of immune related responses of different immunotherapy schemes with or without SABR; Assessing complete response (CR), partial response (PR), and stable disease (SD)
| Count of participants | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Immune Related Stable Disease (irSD) | 2 | 1 | 4 | 7 |
| Immune Related Partial Response (irPR) | 1 | 0 | 0 | 2 |
| Immune Related Progressive Disease (irPD) | 1 | 5 | 5 | 14 |
Patient's change of tumor since intiation of treatment and patient's exhibiting out of field disease control.
| Count of participants | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Abscopal control rate | — | — | 7 | 9 |
| Disease control rate | — | — | 1 | 7 |
Assesses partial response (PR) rate and complete response (CR) rate
| Count of participants | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Objective Response Rate (ORR) | 1 | 0 | 0 | 2 |
| Abscopal response rate (ARR) | NA | NA | 0 | 2 |
Assessing complete response (CR), partial response (PR), and stable disease (SD)
| Count of participants | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Tumor Burden: Disease Control Rate | 3 | 3 | 4 | 11 |
Collected over Baseline to at least 100 days after the last dose of study treatment, up to 5 years.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ipilimumab + BMS-986156 Arm (30 mg/kg) | 2/10 (20%) | 6/10 (60%) | 10/10 (100%) |
| Ipilimumab + BMS-986156 Arm (100 mg/kg) | 3/10 (30%) | 10/10 (100%) | 10/10 (100%) |
| Ipilimumab + BMS-986156 With SBRT Arm | 1/10 (10%) | 5/10 (50%) | 10/10 (100%) |
| Nivolumab + BMS-986156 With SBRT Arm | 3/20 (15%) | 9/20 (45%) | 20/20 (100%) |
| Event | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| Death NOSGeneral disorders | 5/10 | 1/10 | 3/10 | 3/20 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify *General disorders | 3/10 | 2/10 | 1/10 | 1/20 |
| ColitisGastrointestinal disorders | 1/10 | 2/10 | 0/10 | 0/20 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 2/10 | 0/10 | 2/10 | 2/20 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 2/10 | 1/10 | 0/10 | 0/20 |
| Hepatobiliary disorders - Other, specifyGastrointestinal disorders | 0/10 | 0/10 | 2/10 | 2/20 |
| Thromboembolic eventVascular disorders | 2/10 | 0/10 | 0/10 | 0/20 |
| DiarrheaGastrointestinal disorders | 1/10 | 1/10 | 0/10 | 0/20 |
| FatigueGeneral disorders | 1/10 | 0/10 | 0/10 | 0/20 |
| HypercalcemiaMusculoskeletal and connective tissue disorders | 1/10 | 0/10 | 0/10 | 0/20 |
| Event | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm |
|---|---|---|---|---|
| DyspneaRespiratory, thoracic and mediastinal disorders | 7/10 | 2/10 | 10/10 | 10/20 |
| Back painGeneral disorders | 5/10 | 0/10 | 9/10 | 9/20 |
| RashSkin and subcutaneous tissue disorders | 8/10 | 1/10 | 4/10 | 4/20 |
| FatigueGeneral disorders | 7/10 | 2/10 | 7/10 | 7/20 |
| Abdominal painGeneral disorders | 6/10 | 2/10 | 7/10 | 7/20 |
| Chest wall painGeneral disorders | 0/10 | 2/10 | 7/10 | 7/20 |
| AnorexiaGeneral disorders | 5/10 | 3/10 | 6/10 | 6/20 |
| DiarrheaGastrointestinal disorders | 6/10 | 3/10 | 3/10 | 3/20 |
| CoughRespiratory, thoracic and mediastinal disorders | 6/10 | 1/10 | 4/10 | 4/20 |
| Generalized muscle weaknessMusculoskeletal and connective tissue disorders | 6/10 | 0/10 | 4/10 | 4/20 |
| Age, Continuous(years) | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm | Total |
|---|---|---|---|---|---|
| Median | 59 (51 to 71) | 61 (49 to 77) | 65 (52 to 70) | 60 (52 to 68) | 61 (52 to 70) |
| Sex: Female, Male(Participants) | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm | Total |
|---|---|---|---|---|---|
| Female | 6 | 5 | 4 | 5 | 20 |
| Male | 4 | 5 | 6 | 15 | 30 |
| Ethnicity (NIH/OMB)(Participants) | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 0 | 1 | 3 |
| Not Hispanic or Latino | 8 | 10 | 10 | 19 | 47 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 1 | 1 | 3 |
| White | 7 | 10 | 9 | 18 | 44 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 2 | 0 | 0 | 1 | 3 |
| Region of Enrollment(participants) | Ipilimumab + BMS-986156 Arm (30 mg/kg) | Ipilimumab + BMS-986156 Arm (100 mg/kg) | Ipilimumab + BMS-986156 With SBRT Arm | Nivolumab + BMS-986156 With SBRT Arm | Total |
|---|---|---|---|---|---|
| United States | 10 | 10 | 10 | 20 | 50 |
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M.D. Anderson Cancer Center