Protocol Summary

Protocol No.: OCR14653

Sponsor Protocol No.: MK-3475-177

Study Title
A Phase III Study of Pembrolizumab (MK-3475) vs. Chemotherapy in Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (KEYNOTE-177)

Principal Investigator(s)
George, Thomas

Objective
In this study, participants with MSI-H or dMMR advanced colorectal carcinoma will be randomly assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for the treatment of advanced colorectal carcinoma.

Phase: Phase III

Age Group: Adult

Scope: National

Treatment
Arm 1: Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years)

Arm 2: Standard of Care
Per Investigator choice, participants receive 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6 + bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6 + cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI + bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI + cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle.

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 18 years-old and older
2. Locally confirmed dMMR or MSI-H stage IV colorectal carcinoma
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy of at least 3 months
5. Measurable disease
6. Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of SOC therapy or 120 days after the last pembrolizumab dose
7. Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of SOC therapy or 120 days after the last pembrolizumab dose
8. Adequate organ function

EXCLUSION CRITERIA:
1. Has received prior systemic therapy for Stage IV colorectal cancer. May have received prior adjuvant chemotherapy for colorectal cancer as long as it was completed at least 6 months prior to randomization on this study
2. Currently participating and receiving treatment in another study, or participated in a study of an investigational agent and received treatment, or used an investigational device within 4 weeks of randomization
3. Active autoimmune disease that has required systemic treatment in past 2 years
4. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization on this study
5. Radiation therapy within 4 weeks prior to randomization on this study and not recovered to baseline from adverse events due to radiation therapy
6. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
7. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization on this study
8. Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.)
9. Another malignancy that is progressing or requires active treatment with the exception of non-melanomatous skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma
10. Received a live vaccine within 30 days of planned start of study medication
11. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C
12. Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
13. Active infection requiring systemic therapy
14. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
15. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of SOC or 120 days after the last dose of pembrolizumab

Applicable Disease Sites
Colon Cancer

Participating Institutions
UF Gainesville : Margaret Veal

Contact
Margaret Veal
Phone: +1 352-265-0680 ext. 87656

Email: mamcewan@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02563002