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)

Automatisch geschlossen · 2016 bis 2020

Klinische Forschung
Multizentrisch, KSSG als teilnehmendes Zentrum
Automatisch geschlossen
Phase III

Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 42 days, eligible subjects can be randomized to either pembrolizumab (experimental arm) or standard of care chemotherapy (control arm). Subjects will receive pem-brolizumab (MK-3475) beginning on Day 1 of each 3 week dosing cycle or chemotherapy beginning on Day 1 of each 2 week cycle. The chemotherapy to be used must be chosen before randomization.
Subjects will be randomized in a 1:1 fashion to standard chemotherapy per Investigator’s choice or to pembroli-zumab (MK- 3475). Treatment on study will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator’s decision to withdraw the subject, subject withdraws consent, preg-nancy of the subject, noncompliance with trial treatment or procedure requirements, subject receives 35 treatments (approximately 2 years), (pembrolizumab arm only), or administrative reasons requiring cessation of treatment. Subjects who stop pembrolizumab
(MK-3475) as a result of obtaining a centrally confirmed complete response (CR), or after receiving 35 trial treatments (approx. 2 years) and have stable disease (SD) or better may be eligible, at the discretion of the Investigator, for an additional 17 trial treatments (ap-proximately 1 year) after experiencing PD while off pembrolizumab (MK-3475) if they meet the criteria for re- treatment; this will be designated the Second Course Treatment Phase. Subjects randomized to the chemo-therapy arm will have the option to crossover and receive treatment with pembrolizumab (MK-3475) in the Crossover Phase after verification of PD by blinded independent central imaging vendor per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAE) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.
All subjects will have post-treatment follow-up for disease status, until initiating a non-study cancer treatment, experiencing disease progression, death, withdrawing consent, or becoming lost to follow-up.
During the study, subjects may undergo elective resection of the primary tumor and metastasectomy with curative intent if deemed eligible per site institutional standard after achieving a response to trial therapy.