Impact of Circadian Rhythm on Immunotherapy

NCT ID: NCT07224971

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-02
• Study Completion Date: 2030-05-01

Brief Summary

This study aims to determine whether morning versus afternoon treatment impacts efficacy of (standard of care) immunotherapy in a broad patient population. Patients with any type of advanced/metastatic malignancy are eligible to enroll in this study, as long as first-line anti-PD-1/PD-L1 immunotherapy is on label for their condition. Participants will then be randomized to either the early treatment group (administration must start and conclude by 11:00 AM +1 hour window) or the late treatment group (administration must start after 12:00 PM).

Detailed Description

The US market has many FDA approved options for anti-PD-1/PD-L1 immunotherapies, including pembrolizumab, nivolumab, cemiplimab, durvalumab, dostarlimab, avelumab, and atezolizumab, among others that are in development. With an estimated 56.55% of cancer patients eligible for treatment with anti-PD-1/PD-L1 immunotherapy (as of 2023), the impact of timing on immunotherapy efficacy should be delineated in order to provide the best care possible to patients This study will be implemented at a large regional cancer center in the United States. Three patient cohorts will be investigated: Non-Small Cell Lung Cancer (NSCLC) patients who receive first-line ICI therapy (Cohort A), NSCLC patients with stable disease or response after induction therapy receiving maintenance ICI therapy (Cohort B), and solid tumor patients receiving first-line ICI therapy (Cohort C).

To the best the knowledge of this principal investigator, this is the first prospective time-of-day immunotherapy study to take place in the US. Key endpoints include real-world progression free survival (rwPFS)[26], overall survival (OS), safety, quality of life (QoL), and pharmacoeconomic outcomes.

Conditions

Advanced/Metastatic NSCLC

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early Immunotherapy dosing

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 Type: EXPERIMENTAL

Immunotherapy - PD-1 Blocker

Intervention Type: DRUG

Standard of Care Drugs (at investigator's discretion) may include: pembrolizumab, nivolumab, cemiplimab, durvalumab, dostarlimab, avelumab, and atezolizumab, or other immune checkpoint inhibitors used in cancer treatment that targets cancer cells by blocking the PD-1 receptor on T cells.

Late Immunotherapy dosing

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)

Group Type: ACTIVE_COMPARATOR

Immunotherapy - PD-1 Blocker

Intervention Type: DRUG

Standard of Care Drugs (at investigator's discretion) may include: pembrolizumab, nivolumab, cemiplimab, durvalumab, dostarlimab, avelumab, and atezolizumab, or other immune checkpoint inhibitors used in cancer treatment that targets cancer cells by blocking the PD-1 receptor on T cells.

Interventions

Immunotherapy - PD-1 Blocker

Standard of Care Drugs (at investigator's discretion) may include: pembrolizumab, nivolumab, cemiplimab, durvalumab, dostarlimab, avelumab, and atezolizumab, or other immune checkpoint inhibitors used in cancer treatment that targets cancer cells by blocking the PD-1 receptor on T cells.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Liza Villaruz, MD

OTHER

Sponsor Role: lead

Responsible Party

Liza Villaruz, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Liza Villaruz, MD

Role: PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Locations

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jennifer Ruth, RN

Role: CONTACT

ruthj2@upmc.edu

412-623-8963

Facility Contacts

Jennifer Ruth, RN

Role: primary

ruthj2@upmc.edu

412-623-8963

Other Identifiers

HCC 25-127

Identifier Type: -

Identifier Source: org_study_id