Phase I/II Trial of Ipilimumab or Nivolumab With BMS-986156 and Hypofractionated Stereotactic Radiation Therapy in Patients With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Number of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histological confirmation of solid metastatic cancer with at least one metastatic or primary lesion in the liver or lung/chest, except for group
- •Patients who have completed prior systemic anti-cancer therapies, an interval of 5 drug half-lives or 4-weeks whichever is shorter, is required, prior to enrollment on study. Note: patients with anaplastic thyroid will be waived from this inclusion criteria given the rapid trajectory of their disease
- •All patients must have at least one metastatic or primary lesion within the lung/chest or liver located in an anatomical location amenable to SBRT treatment with 50 Gy in 4 fractions or with 60 Gy in 10 fractions, except for group
- •Repeat radiation in fields previously radiated will be allowed at the discretion of the treating physician
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky > 60%)
- •Total bilirubin =< 2.0 mg/dL (does NOT apply to patients with Gilbert's syndrome) (use of growth factors or blood transfusion to achieve these requirements is not allowed 2 weeks prior to study enrollment)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal (use of growth factors or blood transfusion to achieve these requirements is not allowed 2 weeks prior to study enrollment)
- •White blood count (WBC) >= 2500/uL (use of growth factors or blood transfusion to achieve these requirements is not allowed 2 weeks prior to study enrollment)
- •Absolute neutrophil count (ANC) >= 1000/uL (use of growth factors or blood transfusion to achieve these requirements is not allowed 2 weeks prior to study enrollment)
- •Platelets >= 75K (use of growth factors or blood transfusion to achieve these requirements is not allowed 2 weeks prior to study enrollment)
- •Hemoglobin >= 9 g/dL (use of growth factors or blood transfusion to achieve these requirements is not allowed 2 weeks prior to study enrollment)
- •Creatinine =< 2.0 x upper limit of normal (ULN) (use of growth factors or blood transfusion to achieve these requirements is not allowed 2 weeks prior to study enrollment)
- •Patients must be willing and able to review, understand, and provide written consent before starting therapy
- •Patients with brain metastasis will be included as long as they are free of neurologic symptoms related to metastatic brain lesions and who do not require or receive systemic corticosteroid therapy, > 10 mg/day in the 14 days prior to beginning the trial (=< 10 mg steroid, e.g.: prednisone, is allowed). Patients with stable brain metastases (clinically and radiographically) for >= 4 weeks to enroll on the protocol.
- •Patients that have previously progressed on immunotherapy such as ipilimumab, anti-PD-I, anti-PDL-1 or talimogene laherparepvec (T-VEC) will be eligible.
排除标准
- •Serious autoimmune disease at the discretion of the treating attending: patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) are excluded from this study
- •Active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation
- •Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs): e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Known active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C that has not been documented to be stable
- •Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab)
- •Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids while receiving ipilimumab (as long as steroid replacement is significantly greater than what is required for physiologic replacement, i.e. in hypothyroidism)
- •Pregnant women are excluded from this study. Women of child-bearing potential (WOCBP) must have a pregnancy test every 4 weeks and WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of immunotherapy drugs (ipilimumab/nivolumab/BMS-986156), during the course of the treatment and 160 days AFTER the last dose of study drug you should not get pregnant or breast feed. In the case of male participants, during the course of treatment and 220 days AFTER the last dose of immunotherapy you should not father a child (condom use is mandatory, even if vasectomized) or donate sperm. For contraception guidelines please see protocol
- •History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician
- •Prior allogeneic stem cell transplantation
- •Patients who were intolerant to previous immuno-oncology (IO) drugs should be excluded
研究组 & 干预措施
Group I (ipilimumab, BMS-986156, 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. 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.
干预措施: Anti-GITR Agonistic Monoclonal Antibody BMS-986156 (Drug)
Group I (ipilimumab, BMS-986156, 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. 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.
干预措施: Ipilimumab (Biological)
Group I (ipilimumab, BMS-986156, 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. 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.
干预措施: Nivolumab (Biological)
Group II (ipilimumab, BMS-986156, SBRT, 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.
干预措施: Anti-GITR Agonistic Monoclonal Antibody BMS-986156 (Drug)
Group II (ipilimumab, BMS-986156, SBRT, 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.
干预措施: Ipilimumab (Biological)
Group II (ipilimumab, BMS-986156, SBRT, 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.
干预措施: Nivolumab (Biological)
Group II (ipilimumab, BMS-986156, SBRT, 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.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
Group III (nivolumab, BMS-986156, SBRT)
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.
干预措施: Anti-GITR Agonistic Monoclonal Antibody BMS-986156 (Drug)
Group III (nivolumab, BMS-986156, SBRT)
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.
干预措施: Nivolumab (Biological)
Group III (nivolumab, BMS-986156, SBRT)
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.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
结局指标
主要结局
Number of Dose Limiting Toxicities (DLTs)
时间窗: Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0)
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
次要结局
- Assess SBRT and Palliative Radiation Completion(Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0))
- Immune-related Tumor Response(Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0))
- Out-of-field (Abscopal) Disease Control Rate (ACR)(Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0))
- Out-of-field (Abscopal) Response Rate (ARR)(Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0))
- Tumor Burden: Disease Control Rate(Median duration of follow-up 32.3 months (95% CI 8.6 to 56.0))