Это исследование сравнивает утро с случайным планированием стандарта инфузии иммунотерапии ингибитора ингибитора Пембролизумаба у пациентов с метастатическим немелкоклеточным раком легких (TIME-NSCLC)

The intervention in this study is scheduling of the time of pembrolizumab infusions. This group will have their infusion start times restricted to between 0800 AM and 1000 AM .

The intervention in this study is scheduling of the time of pembrolizumab infusions.

This group will undergo randomized scheduling in which infusions are scheduled without respect to a specific time of day. The start time of each infusion that will occur during the study intervention period will be randomized into 1 of 3 time periods: 1000 AM to 1200 PM, 1201 PM to 1400 PM, and 1401 PM to 1700 PM. Randomization of scheduling in the Standard of Care Group approximates the typical ad hoc scheduling of infusion times done as standard of care, with reduction in potential for bias on the part of those involved in scheduling given the unblinded nature of the intervention. The time windows for the Standard of Care group have been chosen to allow infusions to be scheduled throughout the day without overlap with the specific scheduling window of the Morning Group, in order to simplify interpretation of clinical outcomes.

The intervention in this study is scheduling of the time of pembrolizumab infusions.

PFS is defined as the time between the date of treatment initiation and the date of disease progression (determined utilizing RECIST 1.1 criteria) or death (whatever the cause), whichever occurs first. The rate of PFS at 18 weeks will be determined based on the number of participants who remain alive and whose disease has not progressed in each study arm at the 18 weeks imaging assessment. Comparison will be made to the baseline pretreatment computed tomography (CT) +/- magnetic resonance imaging (MRI) scans, to be completed within 6 weeks of treatment start.

Deviation from the scheduling intervention is defined as having occurred when a pembrolizumab infusion is started outside of the pre-specified time window. The deviation rate will be calculated both for all infusions for all study participants together, and for the infusions occurring for the participants in the individual study arms independently.

Participant drop out is defined as voluntary withdrawal from the study prior to completion of study intervention period (between first pembrolizumab infusion and end-of-study visit at Week 19). The dropout rate will be calculated both for all study participants, and for the participants in the individual study arms independently.

PFS is defined as the time between the date of treatment initiation and the date of disease progression (determined utilizing RECIST 1.1 criteria) or death (whatever the cause), whichever occurs first. For participants who remain alive and whose disease has not progressed, PFS will be censored on the date of last survival follow-up assessment at ~1 year after initiation of pembrolizumab treatment. PFS will be based on the disease assessment or date of death provided by the investigator.

OS is defined as the time between the date of treatment initiation and the date of death (whatever the cause)

Objective response rate (ORR) will be determined utilizing RECIST 1.1 criteria (Eisenhauer et al., 2009). Baseline staging diagnostic imaging will be compared to imaging at 18 weeks.

Proportion of patients with all grade or grade 3 or higher treatment related immune-related toxicity as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Analysis of peripheral blood for peripheral cytokine response and phenotyping of the peripheral immune cell repertoire.

Participants in the Standard of Care randomized scheduling group will have a variable amount of their infusion occur in the morning or afternoon. A sensitivity analysis of PFS using the Log-Rank method will be performed including only those patients from the Standard of Care randomized scheduling group who have more than 25%, and more than 50% of their pembrolizumab infusions occurring after 1400 pm