Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07224971

Impact of Circadian Rhythm on Immunotherapy

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).

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Advanced/Metastatic NSCLC Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location status: Recruiting

Location contact

Jennifer Ruth, RN

CONTACT

[email protected]

412-623-8963

Liza Villaruz, MD

PRINCIPAL_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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).

  • 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.
  • 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
  • Must have the ability to understand and the willingness to sign a written informed consent document.
  • Able to read and write in English.

Exclusion criteria

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

Treatment and study plan

Immunotherapy - PD-1 Blocker

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.

Primary outcomes

  1. Real-world progression-free survival (rwPFS) - Cohort A

    Time frame: Up to 4.5 years

    Time from first dose of 1st line treatment to clinician documented clinical disease progression, initiation of new line of therapy, or death from any cause, whichever comes first. Real-world progression-free survival (rwPFS), defined as the time from first dose of 1st line treatment to clinician documented clinical disease progression, initiation of new line of therapy, or death from any cause, whichever came first. Per RECISIT v1.1, Progressive Disease: ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

Secondary outcomes

  1. Overall Survival (OS) - Cohort A

    Time frame: Up to 4.5 years

    Overall Survival (OS) defined as time from first dose of 1st line treatment to death from any cause.

  2. Real-world progression-free survival (rwPFS) - Cohort B

    Time frame: Up to 4.5 years

    Time from first dose of 1st line treatment to clinician documented clinical disease progression, initiation of new line of therapy, or death from any cause, whichever came first. Per RECISIT v1.1, Progressive Disease: ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  3. Real-world progression-free survival (rwPFS) - Cohort C

    Time frame: Up to 4.5 years

    Time from first dose of 1st line treatment to clinician documented clinical disease progression, initiation of new line of therapy, or death from any cause, whichever came first. Per RECISIT v1.1, Progressive Disease: ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  4. Overall Survival (OS) - Cohort B

    Time frame: Up to 4.5 years

    Overall Survival (OS) defined as time from first dose of 1st line treatment to death from any cause.

  5. Overall Survival (OS) - Cohort C

    Time frame: Up to 4.5 years

    Overall Survival (OS) defined as time from first dose of 1st line treatment to death from any cause.

  6. Health Related Quality of Life (HRQoL) - EQ-5D-5L - Cohort A

    Time frame: At Screening - Up to 28 days after signed consent]

    Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.

  7. Health Related Quality of Life (HRQoL) - EQ-5D-5L - Cohort B

    Time frame: At Screening - Up to 28 days after signed consent]

    Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.

  8. Health Related Quality of Life (HRQoL) - EQ-5D-5L - Cohort C

    Time frame: At Screening - Up to 28 days after signed consent]

    Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.

  9. Health Related Quality of Life (HRQoL) - EQ-5D-5L - Cohort A

    Time frame: At Day 1 of Each Treatment Cycle (2-6-week cycles, per specific agent)

    Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.

  10. Health Related Quality of Life (HRQoL) - EQ-5D-5L - Cohort B

    Time frame: At Day 1 of Each Treatment Cycle (2-6-week cycles, per specific agent)

    Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.

  11. Health Related Quality of Life (HRQoL) - EQ-5D-5L - Cohort C

    Time frame: At Day 1 of Each Treatment Cycle (2-6-week cycles, per specific agent)

    Patient reported HRQoL scores using the EQ-5D-5L instrument. EQ-5D-5L is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from each of the five dimensions range from 1 to 5. Total score ranges from 5 to 25, where higher scores indicate worse health status.

Study contacts

Contact information is provided by the study sponsor or research team.

Jennifer Ruth, RN

CONTACT

[email protected]

412-623-8963

Sponsors and collaborators

Lead sponsor

Liza Villaruz, MD

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2030
First posted
Nov 5, 2025
Registry last updated
Dec 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.