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

  • Interventional
  • Not Recruiting
  • NCT02460198
Eligibility Details Visit Clinicaltrials.gov

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)

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.

Gender
All

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

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.

At a Glance

National Government IDNCT02460198

IRB#IRB15-0983

Lead SponsorMerck Sharp & Dohme Corp.

Lead PhysicianBlase Polite

Collaborator(s)N/A

EligibilityAll
18 Years and up
Not Recruiting