This clinical trial is comparing morning infusions of the study drug (pembrolizumab) to random infusion scheduling for patients with non-small cell lung cancer.
Participants will be randomized to either the Intervention (Morning Group) where Infusion start times are restricted between 0800 AM and 1000 AM or to the Control (Standard of Care) group where scheduling will occur as standard of care scheduling, in which infusions are scheduled without respect to a specific time of day.
There are past studies that suggest the timing of treatment may influence immune response and outcomes. This idea is called chronotherapy. Chronotherapy explores the notion that the timing of drug administration in relation to the body's internal clock can optimize treatment effectiveness. The timing of the infusions for the morning group was therefore, chosen based on data from these past studies that looked at circadian variation in immune system function with the intent to focus on similar infusion windows.
The aim of this study is to provide confirmation that the intervention is possible to achieve and use these results to design a larger study. Circadian timing of drug administration, if effective, would represent an intervention that could improve survival outcomes at no additional cost or apparent increase in toxicity, which is truly rare in oncology.
Participants are asked to participate in the study intervention for 18 weeks (6 cycles of pembrolizumab), after which participants would continue with ad hoc scheduling as per standard of care.
Patients with histologic diagnosis mNSCLC with PDL1 staining ≥ 50% on standard of care IHC testing
Patients must be eligible for treatment with standard-of-care pembrolizumab
Patients must be 18 years of age or older.
Patients must be capable of providing consent to enrolment and willing to comply with study, treatment and follow-up.
Concurrent therapy with systemic therapy other than pembrolizumab (such as chemotherapy, targeted therapy, other checkpoint inhibitors, or hormonal therapy).
Treatment plan includes local therapy such as radiation or surgery.
Untreated symptomatic brain metastases, or previously treated brain metastases requiring corticosteroids for symptom control. Patients with untreated asymptomatic brain metastases, where all lesions are < 2cm in size with no vasogenic edema, are eligible.
Presence of leptomeningeal disease.
Parallel
Scheduling of the time of pembrolizumab infusions
DrugThe intervention in this study is scheduling of the time of pembrolizumab infusions.
Rate of progression free survival at 18 weeks
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.
Rate of deviation from scheduling intervention
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.
Dropout Rate
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.
Progression free survival
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.
Overall survival
OS is defined as the time between the date of treatment initiation and the date of death (whatever the cause)
Objective response rate at 18 weeks
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.
Treatment-related toxicity
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.
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