Description:
In this study, participants with previously-treated locally-advanced unresectable or
metastatic mismatched repair (MMR) deficient or microsatellite instability-high (MSI-H)
colorectal carcinoma (CRC) will be treated with pembrolizumab (MK-3475, KEYTRUDA®)
monotherapy.
There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, participants
are required to have been previously treated with standard therapies, which must include
fluoropyrimidine, oxaliplatin, and irinotecan. Enrollment into Cohort A has been completed.
For Cohort B, participants are required to have been previously treated with at least one
line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine
+ irinotecan +/ - anti-vascular endothelial growth factor (VEGF)/ epidermal growth factor
regulator (EGFR) monoclonal antibody.
The primary hypothesis is that Objective Response Rate (ORR) based on Response Evaluation
Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor in
participants with locally advanced unresectable or metastatic MMR deficient or MSI high CRC
is greater than 15%.
Title
- Brief Title: Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164)
- Official Title: A Phase II Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects With Previously Treated Locally Advanced Unresectable or Metastatic (Stage IV) Mismatched Repair Deficient or Microsatellite Instability-High Colorectal Carcinoma (KEYNOTE-164)
Clinical Trial IDs
- ORG STUDY ID:
3475-164
- SECONDARY ID:
2015-001852-32
- SECONDARY ID:
153046
- SECONDARY ID:
MK-3475-164
- SECONDARY ID:
KEYNOTE-164
- NCT ID:
NCT02460198
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab | MK-3475, KEYTRUDA® | Cohort A - Pembrolizumab 200 mg |
Purpose
In this study, participants with previously-treated locally-advanced unresectable or
metastatic mismatched repair (MMR) deficient or microsatellite instability-high (MSI-H)
colorectal carcinoma (CRC) will be treated with pembrolizumab (MK-3475, KEYTRUDA®)
monotherapy.
There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, participants
are required to have been previously treated with standard therapies, which must include
fluoropyrimidine, oxaliplatin, and irinotecan. Enrollment into Cohort A has been completed.
For Cohort B, participants are required to have been previously treated with at least one
line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine
+ irinotecan +/ - anti-vascular endothelial growth factor (VEGF)/ epidermal growth factor
regulator (EGFR) monoclonal antibody.
The primary hypothesis is that Objective Response Rate (ORR) based on Response Evaluation
Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor in
participants with locally advanced unresectable or metastatic MMR deficient or MSI high CRC
is greater than 15%.
Detailed Description
With protocol amendment 08 (13-Nov-2019), once study participants have achieved the study
objective or the study has ended, participants will be discontinued from this study and may
be enrolled in a pembrolizumab extension study (NCT03486873) to continue protocol-defined
assessments and treatment.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort A - Pembrolizumab 200 mg | Experimental | Participants were previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan. Cohort A participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 3-week cycle (Q3W) for up to approximately 52 cycles (up to approximately 4 years). | |
Cohort B - Pembrolizumab 200 mg | Experimental | Participants were previously treated with at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/ - anti vascular endothelial growth factor (VEGF)/ epidermal growth factor regulator (EGFR) monoclonal antibody. Cohort B participants receive pembrolizumab 200 mg IV on Day 1 Q3W for up to approximately 52 cycles (up to approximately 4 years). | |
Eligibility Criteria
Inclusion criteria:
- Histologically-proven locally advanced unresectable or metastatic colorectal carcinoma
- Locally confirmed MMR deficient or MSI-H status
- Has been previously treated with standard therapies, which must include, for Cohort A,
fluoropyrimidine, oxaliplatin, and irinotecan, and for Cohort B, at least one line of
systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine
+ irinotecan +/- anti-VEGF/EGFR monoclonal antibody (mAb).
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Life expectancy of greater than 3 months
- Provides an archival or newly obtained (≤60 days prior to first dose of study
treatment) tumor tissue sample (Cohort B)
- At least one measurable lesion
- Female participants of childbearing potential should be willing to use acceptable
methods of contraception or be surgically sterile, or abstain from heterosexual
activity for the course of the study through 120 days after the last dose of study
treatment
- Male participants should agree to use an adequate method of contraception starting
with the first dose of study treatment through 120 days after the last dose of study
treatment
- Adequate organ function
Exclusion criteria:
- Currently participating in another study and receiving trial treatment, participated
in a study of an investigational agent and received trial treatment within 4 weeks of
the first dose of treatment in this study, or used an investigational device within 4
weeks of the first dose of treatment in this study
- Active autoimmune disease that has required systemic treatment in past 2 years
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment
- Known active central nervous system metastases and/or carcinomatous meningitis
- Prior monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or
radiation therapy within 2 weeks prior to study Day 1 or not recovered (i.e., ≤ Grade
1 or at baseline) from adverse events (AEs) due to a previously administered agent
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.
- Received a live vaccine within 30 days of planned start of study treatment
- Known history of human immunodeficiency virus (HIV)
- Known active Hepatitis B or C
- Has known history of, or any evidence of interstitial lung disease or active,
noninfectious pneumonitis
- Active infection requiring systemic therapy
- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study
- Pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study treatment
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective Response Rate (ORR) - Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) Assessed by Central Imaging Vendor |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | Objective response rate was defined as the percentage of the participants in the analysis population who had a complete response (CR) or partial response (PR). Complete Response: disappearance of all target lesions. Partial Response: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responses were based upon blinded central imaging vendor per RECIST 1.1. The point estimate and 95% confidence interval for the ORR, were provided using an exact binomial distribution (Clopper and Pearson method). Participants without response data were counted as nonresponders. The data cutoff date was 09-SEP-2019. |
Secondary Outcome Measures
Measure: | Disease Control Rate (DCR) Per RECIST 1.1 Assessed by Central Imaging Vendor. |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | Disease Control Rate was defined as the percentage of participants who achieved confirmed CR or PR or had demonstrated stable disease (SD) for at least 24 weeks prior to any evidence of progression. Complete Response: disappearance of all target lesions. Partial Response: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. or the appearance of new lesion(s). Participants in the analysis population with missing DCR were considered as disease not under control. The data cutoff date was 09-SEP-2019. |
Measure: | Progression-Free Survival (PFS) Per RECIST 1.1 Assessed by Central Imaging Vendor. |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | PFS is defined as the time from first day of study treatment to the first documented disease progression or death due to any cause, whichever occurs first. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions was also considered progression). PFS was summarized by Kaplan-Meier (KM) methods. The data cutoff date was 09-SEP-2019. |
Measure: | Overall Survival (OS) |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | OS is defined as the time from first day of study treatment to death due to any cause. Participants without documented death at the time of analysis are censored at the date of the last follow-up. OS was summarized by Kaplan-Meier (KM) methods. The data cutoff date was 09-SEP-2019. |
Measure: | Number of Participants Who Experienced an Adverse Event (AE). |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. |
Measure: | Number of Participants Who Discontinued Study Treatment Due to an AE. |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. |
Measure: | Duration of Response (DOR) Per RECIST 1.1 as Assessed by the Central Imaging Vendor |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | For participants who demonstrated a CR or PR, duration of response was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurred first. Complete Response: disappearance of all target lesions. Partial Response: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responses were based upon blinded central imaging vendor per RECIST 1.1. Duration of Response was based on IRC review using RECIST 1.1 and was summarized by Kaplan-Meier (KM) methods for censored data. Nonresponders were excluded from the analysis of DOR. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial Keywords
- Programmed Cell Death-1 (PD1, PD-1)
- Programmed Death-Ligand 1 (PDL1, PD-L1)
- MSI-H
- MSI
Last Updated
March 22, 2021