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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
113
MK-3475 10 mg/kg every 14 days
Stanford University
Stanford, California, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Investigator Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, NIH
Bethesda, Maryland, United States
Ohio State University
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
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.
Time frame: 20 weeks
Immune-related Objective Response Rate in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
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.
Time frame: 28 months
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
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.
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Columbus, Ohio, United States
Providence Portland Medical Center
Portland, Oregon, United States
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States
Time frame: 20 weeks
Objective Response Rate in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
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.
Time frame: 28 months
Progression Free Survival (PFS) at 20 Weeks in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
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.
Time frame: 20 weeks
Overall Survival (OS)
OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Time frame: 4 years
Immune-related Progression Free Survival (irPFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Immune Related Response Criteria (irRC)
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 28 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.
Time frame: 28 weeks
Objective Response Rate (ORR) in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
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.
Time frame: 28 months
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
When calculating the incidence of AEs, each adverse event (AE) (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Time frame: 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)
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 28 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.
Time frame: 28 weeks
Disease Control Rate in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Disease Control Rate (DCR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, 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.
Time frame: 28 months
Does MSI as a Marker Predict Treatment Response
ORR was used to determine whether MSI is a marker that predicts treatment response. This is the same data presented in outcome measure number 8 (ORR, to test against null of 5%).
Time frame: 28 months