Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 7
- 主要终点
- Immune-related Objective Response Rate in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
研究概览
简要总结
This study will be looking at whether MK-3475 (an antibody that blocks negative signals to T cells) is effective (anti-tumor activity) and safe in three different patient populations. These include: 1. patients with MSI positive colon cancer, 2. patients with MSI negative colon cancer and 3. patients with other MSI positive 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
- •Cohort A only: Patients with microsatellite instability (MSI) positive colorectal cancer
- •Cohort B only: Patients with MSI negative colorectal cancer
- •Cohort C only: Patients with MSI positive non-colorectal cancer -
- •Have measurable disease
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
- •Adequate organ function as defined by study-specified laboratory tests
- •Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
- •Signed informed consent form
- •Willing and able to comply with study procedures
- •Agree to have a biopsy of participants' cancer
- •Patients with colon cancer must have received at least two prior cancer therapy regimens.
- •Patients with other cancer types must have received at least one prior cancer therapy
- •Progressive disease
排除标准
- •Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements.
- •Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
- •Patients who have had radiation within 2 weeks prior to the first dose of study drug
- •Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
- •Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
- •Patients who have received any of the following concomitant therapy: Interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids within one week prior to first dose of study drug
- •Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 (exception: inactivated flu vaccines)
- •Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration
- •Patient who have had prior treatment with anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
- •Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis, central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin.
- •Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
- •Patients with evidence of interstitial lung disease
- •Systemically active steroid use
- •Patients on home oxygen
- •Patients with oxygen saturation of <92% on room air by pulse oximetry
- •Pregnant or lactating
- •Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
- •Patient with known active central nervous system metastases and/or carcinomatous meningitis.
- •Patients with primary brain tumors.
- •Requires any other form of systemic or localized antineoplastic therapy while on study
- •Has any tissue or organ allograft
- •Patients with history of allogeneic hematopoeitic stem cell transplant
研究组 & 干预措施
Cohort A: MSI Positive Colorectal Cancer
干预措施: MK-3475 (Drug)
Cohort B: MSI Negative Colorectal Cancer
干预措施: MK-3475 (Drug)
Cohort C: MSI Positive Non-Colorectal Cancer
干预措施: MK-3475 (Drug)
结局指标
主要结局
Immune-related Objective Response Rate in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
时间窗: 28 months
For Cohorts A and B: Immune-related Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation.
Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive Non-colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
时间窗: 20 weeks
For Cohort C: irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.
Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
时间窗: 20 weeks
For Cohorts A and B: irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.
Progression Free Survival (PFS) at 20 Weeks in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
时间窗: 20 weeks
For Cohorts A and C: PFS is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 20 weeks. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Objective Response Rate in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
时间窗: 28 months
For Cohorts A and C: Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.
次要结局
- Does MSI as a Marker Predict Treatment Response(28 months)
- Overall Survival (OS)(4 years)
- Disease Control Rate in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(28 months)
- Immune-related Progression Free Survival (irPFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Immune Related Response Criteria (irRC)(28 weeks)
- Objective Response Rate (ORR) in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(28 months)
- Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity(28 months)
- Progression Free Survival (PFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(28 weeks)