Impact of Circadian Rhythm on Immunotherapy

NCT07224971 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 25-127
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 1

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).

Conditions

Advanced/Metastatic NSCLC

Keywords

anti-PD-1/PD-L1 Immunotherapy; Circadian Rhythm

Outcome Measures

Primary Outcomes (1)

• Real-world progression-free survival (rwPFS) - Cohort A

  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.

  Up to 4.5 years

Secondary Outcomes (11)

• Overall Survival (OS) - Cohort A

  Up to 4.5 years

• Real-world progression-free survival (rwPFS) - Cohort B

  Up to 4.5 years

• Real-world progression-free survival (rwPFS) - Cohort C

  Up to 4.5 years

• Overall Survival (OS) - Cohort B

  Up to 4.5 years

• Overall Survival (OS) - Cohort C

  Up to 4.5 years

Study Arms (2)

Early Immunotherapy dosing

EXPERIMENTAL

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)

Drug: Immunotherapy - PD-1 Blocker

Late Immunotherapy dosing

ACTIVE COMPARATOR

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)

Drug: Immunotherapy - PD-1 Blocker

Interventions

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.

Early Immunotherapy dosing; Late Immunotherapy dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Liza Villaruz, MD: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Liza Villaruz, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Ruth, RN

CONTACT

412-623-8963; ruthj2@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 31, 2025
• First Posted: November 5, 2025
• Study Start: December 2, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2030
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)