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)

Phase 3

Completed

Conditions: colon cancer
rectum cancer
10017991

Registration Number: NL-OMON54608

Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

1. Provide documented informed consent for the study.
2. Be male or female who is >= 18 years of age on the date of signing informed
consent.
3. Have locally confirmed MMR deficient (dMMR) or microsatellite instability
high (MSI-H) stage IV colorectal carcinoma
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1 within 10 days prior to treatment initiation.
5. Have life expectancy of at least 3 months
6. Have measurable disease at baseline based on RECIST 1.1 as determined by the
local site Investigator/radiology assessment.
7. Female subjects of childbearing potential must have a negative serum
pregnancy test within 72 hours prior to receiving the first dose of study
medication.
8. Female subjects of childbearing potential must be willing to use an adequate
method of contraception for the course of the study starting with the first
dose of study medication through 180 days after the last dose of study
medication for the chemotherapy arm and 120 days for pembrolizumab arm,
whichever is later.
9. Male subjects of childbearing potential must agree to use an adequate method
of contraception as outlined in Section 5.7.2 - Contraception, starting with
the first dose of study medication through 180 days after the last dose of
study medication for the chemotherapy arm (no contraception requirement for
pembrolizumab MK-3475 arm).
10. Demonstrate adequate organ function. All screening laboratory assessment
should be performed within 10 days prior to treatment initiation.

Exclusion Criteria

1. Has received prior systemic therapy for stage IV CRC. Subjects may have
received prior adjuvant chemotherapy for CRC as long as it was completed at
least 6 months prior to randomization.
2. Is currently participating and receiving study medication in another study,
or has participated in a study of an investigational agent and received study
medication, or used an investigational device within 4 weeks of randomization.
3. Has an active autoimmune disease that has required systemic treatment in
past 2 years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to
randomization.
5. Has had radiation therapy within 4 weeks prior to randomization of study
medication and who has not recovered to baseline from adverse events due to
radiation therapy. Subjects who have been given palliative radiotherapy to
peripheral sites (e.g., bone metastasis) may enter the study before 4 weeks
have elapsed but must have recovered from any acute adverse effects.
6. Has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may
participate provided they have stable brain metastases [without evidence of
progression by imaging as confirmed by magnetic resonance imaging (MRI) if MRI
was used at prior imaging, or confirmed by computed tomography (CT) imaging if
CT used at prior imaging] at least four weeks prior to the first dose of study
medication; also, any neurologic symptoms must have returned to baseline], and
have not used steroids for brain metastases for at least 28 days prior to trial
initiation. This exception does not include carcinomatous meningitis, as
subjects with carcinomatous meningitis are excluded regardless of clinical
stability.
7. Has had major surgical procedure, open biopsy or significant traumatic
injury within 28 days prior to randomization.
8. Has received prior therapy with an immune checkpoint inhibitor (e.g.,
anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent, etc).
9. Has another malignancy that is progressing or requires active treatment.
Exceptions include non-melanomatous skin cancer that has undergone potentially
curative therapy and in situ cervical carcinoma.
10. Has received a live vaccine within 30 days of planned start of study
medication.
11. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
subject*s participation for the full duration of the study, or is not in the
best interest of the subject to participate, in the opinion of the treating
Investigator.
12. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or
Hepatitis C (e.g., HCV RNA [qualitative] is detected).
13. Has known history of, or any evidence of interstitial lung disease or
active, non-infectious pneumonitis.
14. Has a known

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>This study will use PFS as the primary endpoint. PFS is an acceptable measure<br /><br>of clinical benefit for a randomized phase III trial that demonstrates<br /><br>superiority of a new antineoplastic therapy, especially if the magnitude of<br /><br>effect is large and the therapy has an acceptable risk-benefit profile. </p><br>

Secondary Outcome Measures