Impact of Circadian Rhythm on Immunotherapy

Liza Villaruz, MD

Status and phase: Enrolling; Phase 2

Conditions: Advanced/Metastatic NSCLC

Treatments: Drug: Immunotherapy - PD-1 Blocker

Study type: Interventional

Funder types: Other

Identifiers

NCT07224971

HCC 25-127

Details and patient eligibility

About

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).

Full 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.

Enrollment: 350 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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350 participants in 2 patient groups

Early Immunotherapy dosing

Experimental group

Description:

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)

Treatment:

Drug: Immunotherapy - PD-1 Blocker

Late Immunotherapy dosing

Active Comparator group

Description:

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)

Treatment:

Drug: Immunotherapy - PD-1 Blocker