Immunotherapy Timing for Lung Cancer

Overseen By Jennifer Ruth, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Liza Villaruz, MD

Must be taking: Anti-PD-1/PD-L1

Disqualifiers: Allergic to therapy ingredients

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 2-6 weeks per cycle, ongoing

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether the timing of immunotherapy treatment affects its effectiveness for individuals with advanced lung cancer or other solid tumors. Participants will receive a PD-1 blocker, a type of immunotherapy, either in the morning or afternoon to determine if timing influences treatment outcomes. Individuals with advanced lung cancer or solid tumors who have not yet received immunotherapy, or who qualify for maintenance therapy, may be suitable candidates. Participants must be willing to receive treatment at a specific time of day and meet certain medical criteria. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that PD-1 blockers are generally safe and effective for treating advanced lung cancer. Studies have found that treatments like pembrolizumab and nivolumab can extend patients' lives and shrink tumors. In these studies, patients typically experienced manageable side effects. Some individuals did encounter immune-related side effects, but these were often mild or moderate. The FDA has already approved these treatments for similar conditions, indicating a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the timing of immunotherapy doses, which may impact their effectiveness against lung cancer. Most treatments for lung cancer, like chemotherapy, work by killing fast-growing cells, but this study examines the potential benefits of administering a PD-1 blocker, a type of immunotherapy, at different times of the day. By comparing early morning doses to afternoon doses, researchers hope to discover if the body's biological clock can influence the treatment's success. This could lead to more personalized treatment schedules, potentially improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that PD-1 blockers, like pembrolizumab, effectively treat non-small cell lung cancer (NSCLC). These treatments can extend patients' lives by inhibiting cancer cell growth. In this trial, participants will be assigned to different arms based on the timing of their treatment. Some will receive early immunotherapy dosing, while others will receive late immunotherapy dosing. Some studies suggest that earlier treatment in the day might enhance effectiveness. Specifically, patients treated earlier demonstrated better outcomes than those treated later. This suggests that both the treatment and its timing can be crucial for achieving the best results. ^{4 6 7 8 9}

Who Is on the Research Team?

Liza Villaruz, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is open to patients with any advanced or metastatic cancer where first-line anti-PD-1/PD-L1 immunotherapy is an approved treatment. Participants will be randomly assigned to receive their treatments either in the morning (before 11:00 AM) or in the afternoon (after 12:00 PM).

Inclusion Criteria

Must be willing to be randomized to complete therapy at assigned time of day, which may be early in the morning OR later in the day/into the evening

I am eligible for anti-PD-1/PD-L1 therapy as per my doctor's judgment.

Must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I am allergic to anti-PD-1/PD-L1 therapy or its ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-PD-1/PD-L1 immunotherapy either early in the day (before 11 AM) or late in the day (after 12 PM) based on randomization

2-6 weeks per cycle, ongoing

At Day 1 of each treatment cycle

Follow-up

Participants are monitored for safety, progression-free survival, and overall survival after treatment

Up to 4.5 years

What Are the Treatments Tested in This Trial?

Interventions

• PD-1 Blocker

Trial Overview The study investigates if the time of day when immunotherapy is administered affects its effectiveness. Patients are given a PD-1 blocker, which is a standard care immunotherapy, and are split into two groups based on treatment timing.

How Is the Trial Designed?

Group I: Early Immunotherapy dosing Experimental Treatment 1 Intervention

NSCLC and solid tumor patients who receive first-line or ICI therapy early in the day (prior to 11AM) versus late in the day (after 12PM) and NSCLC patients with stable or response disease after induction therapy receiving maintenance ICI therapy early in the day (prior to 11AM) versus late in the day (after 12PM)

Group II: Late Immunotherapy dosing Active Control 1 Intervention

NSCLC and solid tumor patients who receive first-line or ICI therapy late in the day (started after 12 PM) and NSCLC patients with stable or response disease after induction therapy receiving maintenance ICI therapy late in the day (started after 12PM)

Who Is Running the Clinical Trial?

Liza Villaruz, MD

Lead Sponsor

Trials

4

Recruited

40+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925005337

Timing of first pembrolizumab infusion and long-term ... We aimed to evaluate whether the timing of the first pembrolizumab infusion affects outcomes in unresectable non-small cell lung cancer (NSCLC).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11893323/

Overall survival according to time-of-day of combined immuno ... Early time-of-day administration (ToDA) of singe-agent ICIs has been associated with improved overall survival (OS) in patients with metastatic ...

3. jitc.bmj.com jitc.bmj.com/content/13/6/e011622

A real-world study on the efficacy and safety of low-dose ... Low-dose PD-1 monoclonal antibody therapy demonstrated comparable efficacy to standard-dose therapy with a lower incidence of severe irAEs in combination ...

4. spandidos-publications.com spandidos-publications.com/10.3892/ol.2025.14903

Comparative efficacy and safety of first‑line PD‑1/PD‑L1 ... PD-1/PD-L1 inhibitors, especially tislelizumab, pembrolizumab and nivolumab, were effective first-line treatments for NSCLC, providing survival benefits.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7522661/

PD-1/PD-L1 Inhibitors for Non–Small Cell Lung Cancer PD-1 and PD-L1 inhibitors reduce NSCLC growth and improve patient survival by preventing binding of PD-L1 ligands with PD-1 receptors expressed on tumor cells ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12184348/

A real-world study on the efficacy and safety of low-dose ... Low-dose PD-1 monoclonal antibody therapy demonstrated comparable efficacy to standard-dose therapy with a lower incidence of severe irAEs in combination ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405844023017735

Anti-PD-(L)1 therapy of non-small cell lung cancer–A ... Anti-PD-(L)1 is a safe and an effective strategy in patients with advanced/metastatic NSCLC. Clinical responses to nivolumab and pembrolizumab, in particular, ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1606774

Pembrolizumab versus Chemotherapy for PD-L1–Positive ... The results of this randomized trial showed the superiority of anti–PD-1 therapy over platinum-based combination chemotherapy as first-line ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4741366/

PD-1/PD-L1 blockades in non-small-cell lung cancer therapy Immune checkpoint blockade, especially blockade of programmed death-1 (PD-1) receptor and its ligand PD-L1, achieved robust responses and improved survival for ...