Morning versus afternoon immunotherapy for advanced/metastatic NSCLC

Assessing the Impact of Circadian Rhythm on Anti-PD-1/PD-L1 Immunotherapy

This trial will try whether giving first-line anti-PD-1/PD-L1 immunotherapy in the morning versus later in the day improves outcomes for people with advanced or metastatic non-small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 350 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Drugs / interventions: immunotherapy, pembrolizumab, nivolumab, cemiplimab, durvalumab, dostarlimab, avelumab, atezolizumab
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT07224971 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 study assigns patients to receive standard-of-care anti-PD-1/PD-L1 immunotherapy either in an early-morning window or in a later-day window and follows clinical outcomes. Three cohorts are included: first-line NSCLC, NSCLC on maintenance after induction, and first-line treatment for other advanced solid tumors. Key endpoints include real-world progression-free survival, overall survival, safety, quality of life, and pharmacoeconomic measures. The protocol is implemented at a large regional U.S. cancer center and uses FDA-approved PD-1/PD-L1 agents such as pembrolizumab, nivolumab, cemiplimab, durvalumab, dostarlimab, avelumab, and atezolizumab when on-label.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced/metastatic NSCLC eligible for first-line PD-1/PD-L1 therapy (cohort A), NSCLC patients eligible for maintenance after induction response (cohort B), or patients with other advanced solid tumors eligible for first-line PD-1/PD-L1 therapy (cohort C).

Not a fit: Patients who have previously received immune checkpoint inhibitors, whose condition does not have on-label first-line PD-1/PD-L1 therapy, or who cannot adhere to the assigned infusion time window are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, scheduling immunotherapy by time of day could improve survival or tolerability and help clinics optimize treatment delivery.

How similar studies have performed: Retrospective and observational reports have suggested time-of-day effects on immune responses and cancer outcomes, but prospective randomized data are limited and this is among the first U.S. randomized efforts.

Eligibility criteria

Inclusion Criteria:

1. Cohort Specific Criteria

   * Cohort A: Advanced/metastatic NSCLC patients for which 1st line PD-1/PD-L1 therapy is on-label either alone or in combination.
   * Cohort B: Advanced/metastatic NSCLC patients who have completed up to 4 cycles of induction therapy who have stable disease or responsive disease and for which maintenance anti-PD-1/PD-L1 therapy is on-label either alone or in combination.
   * Cohort C: Advanced/metastatic solid tumor malignancy for which first-line anti-PD-1/PD-L1 therapy is on-label either alone or in combination.
2. Prior and concurrent therapy criteria

   o Patients should be ICI-naïve (this should be first-line therapy) (Cohorts A and C), or should have received ICI induction therapy and are now eligible for ICI maintenance therapy (Cohort B).
3. 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.
4. Must be eligible to receive anti-PD-1/PD-L1 therapy singly or in combination with other FDA-approved agents according to standard of care practices, as determined by the clinical judgment of the investigator but according to approved label indications
5. Must have the ability to understand and the willingness to sign a written informed consent document.
6. Able to read and write in English.

Exclusion Criteria:

1\. Participant unable to receive anti-PD-1/PD-L1 therapy due to prior allergic reactions to therapy or any therapy ingredients.

Where this trial is running

Pittsburgh, Pennsylvania

• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Liza Villaruz, MD — UPMC Hillman Cancer Center
• Study coordinator: Jennifer Ruth, RN

Conditions Advanced/Metastatic NSCLC; anti-PD-1/PD-L1 Immunotherapy; Circadian Rhythm