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Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164)

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ClinicalTrials.gov Identifier: NCT02460198
Recruitment Status : Active, not recruiting
First Posted : June 2, 2015
Last Update Posted : January 12, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Colorectal Carcinoma Biological: Pembrolizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 25, 2015
Estimated Primary Completion Date : September 9, 2019
Estimated Study Completion Date : September 9, 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Cohort A: Pembrolizumab
Cohort A participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 3-week cycle (Q3W) for up to 35 cycles (up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Name: MK-3475
Experimental: Cohort B: Pembrolizumab
Cohort B participants receive pembrolizumab 200 mg IV on Day 1 Q3W for up to 35 cycles (up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Name: MK-3475



Primary Outcome Measures :
  1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor [ Time Frame: Up to approximately 2 years ]

Secondary Outcome Measures :
  1. Disease Control Rate (DCR) per RECIST 1.1 assessed by central imaging vendor [ Time Frame: Up to approximately 2 years ]
  2. Duration of Response (DOR) per RECIST 1.1 assessed by central imaging vendor [ Time Frame: Up to approximately 2 years ]
  3. Progression-Free Survival (PFS) per RECIST 1.1 assessed by central imaging vedor [ Time Frame: Up to approximately 2 years ]
  4. Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
  5. Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
  6. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Histologically-proven locally advanced unresectable or metastatic high 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 measureable lesion.
  • Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication .
  • Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study medication.
  • 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 medication in this study, or used an investigational device within 4 weeks of the first dose of medication in this study.
  • Active autoimmune disease that has required systemic treatment in past 2 years .
  • Diagnosis of immunodeficiency or is receiving systemic steroid therapy in dosing exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Known active central nervous system metastases and/or carcinomatous meningitis.
  • Prior 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 AEs due to a previously administered agent.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, OR other immune check point agonist/inhibitor.
  • Has a known additional malignancy that is progressing or requires active treatment within the past 3 years. 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 medication
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or C
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Active infection requiring systemic therapy.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • 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 medication.

Has a history of severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02460198


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02460198     History of Changes
Other Study ID Numbers: 3475-164
2015-001852-32 ( EudraCT Number )
153046 ( Registry Identifier: JAPIC-CTI )
MK-3475-164 ( Other Identifier: Merck Protocol Number )
First Posted: June 2, 2015    Key Record Dates
Last Update Posted: January 12, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1
MSI-H
MSI

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Microsatellite Instability
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Genomic Instability
Pathologic Processes
Pembrolizumab
Antineoplastic Agents