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.
Completed
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| MK-3475 | Cohort A: MSI Positive Colorectal Cancer |
| Name | Type | Description | Interventions |
|---|---|---|---|
| Cohort A: MSI Positive Colorectal Cancer | Experimental |
| |
| Cohort B: MSI Negative Colorectal Cancer | Experimental |
| |
| Cohort C: MSI Positive Non-Colorectal Cancer | Experimental |
|
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | 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 |
| Time Frame: | 20 weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival (OS) |
| Time Frame: | 4 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Immune-related Progression Free Survival (irPFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Immune Related Response Criteria (irRC) |
| Time Frame: | 28 weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Objective Response Rate (ORR) in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
| Time Frame: | 28 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity |
| Time Frame: | 28 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Time Frame: | 28 weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Disease Control Rate in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
| Time Frame: | 28 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Does MSI as a Marker Predict Treatment Response |
| Time Frame: | 28 months |
| Safety Issue: | |
| Description: | 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%). |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
February 6, 2020
