Effects of Infusion Timing on Treatment Response in Solid Tumors (TIMED)

Timing of Immunotherapy and Effective Administration (TIMED): Effects of Infusion Timing on Treatment Response in Solid Tumors

This study evaluates whether the time of day when immunotherapy is given affects clinical outcomes. It includes patients eligible for PD-1 (programmed cell death protein 1) or PD-L1 (programmed death-ligand 1) inhibitor treatment who have either advanced or metastatic non-small cell lung cancer (NSCLC) or locally advanced, resectable head and neck squamous cell carcinoma (HNSCC).The study tests the hypothesis that outcomes differ based on infusion timing (morning versus afternoon). Patients are divided into two cohorts by disease type: Cohort 1 includes NSCLC and Cohort 2 includes HNSCC. Within each cohort, patients are randomly assigned to receive infusions in the morning or afternoon, using a 2:1 ratio for NSCLC and a 1:1 ratio for HNSCC. All treatment and disease assessments follow standard medical care, and outcomes such as survival and treatment response are collected from medical records. Patients will be followed for up to 2 years.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Cancer; Lung Cancer; Metastatic Lung Cancer; Non-small Cell Lung Cancer; Metastatic Head and Neck Cancer; Metastatic Squamous Cell Carcinoma; Resectable Head and Neck Squamous-cell Carcinoma
• Intervention / Treatment: Drug: PD-1/PD-L1 inhibitor monotherapy - 4 cycles before 12:00PM; Drug: PD-1/PD-L1 inhibitor monotherapy - 4 cycles after 3 PM; Drug: PD-1 inhibitor monotherapy - 2 cycles before 12:00PM; Drug: PD-1 inhibitor monotherapy - 2 cycles after 3 PM

• Study Type: Interventional
• Enrollment (Estimated): 238
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Adrianna Warner; Phone Number: 919-984-0000; Email: Adrianna_warner@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill, Department of Radiation Oncology
      • Contact: Adrianna Warner; Phone Number: 919-984-0000; Email: Adrianna_warner@med.unc.edu
      • Principal Investigator: Shetal A Patel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Cohort 1A and 1B:

• Participants with metastatic non-small cell lung cancer (NSCLC).
• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
• Subject is willing and able to comply with study procedures based on the judgement of the investigator.
• Age ≥ 18 years at the time of consent.

Cohort 2A and 2B:

• Participants with resectable head and neck squamous cell carcinoma (HNSCC)
• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
• Subject is willing and able to comply with study procedures based on the judgement
• of the investigator.
• Age ≥ 18 years at the time of consent.

Exclusion Criteria: For All Cohorts (1A,1B, 2A, 2B)

• Subject is currently using steroids (prednisone ≥10 mg or its equivalent) and that cannot be discontinued at least 7 days before starting standard of care treatment.
• Prior ICI (PD-1/PD-L1/CTLA4) treatment received less than 6 months from the time of screening.
• Subject is participating in another treatment clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1A: NSCLC received Anti- PD-1/PD-L1 start prior 12:00 PM; Patients with advanced or metastatic non-small cell lung cancer (NSCLC) eligible for standard-of-care anti-PD-1 (programmed cell death protein 1) or PD-L1 (programmed death-ligand 1) therapy received treatment before 12:00 PM.	Drug: PD-1/PD-L1 inhibitor monotherapy - 4 cycles before 12:00PM; PD-1 (programmed cell death protein 1) or PD-L1 (programmed death-ligand 1) inhibitor monotherapy will be administered before 12:00PM for 4 cycles.
Experimental: Cohort 1B: NSCLC received Anti- PD-1/PD-L1 start after 3:00 PM; Patients with advanced or metastatic non-small cell lung cancer (NSCLC) eligible for standard-of-care anti-PD-1 (programmed cell death protein 1) or PD-L1 (programmed death-ligand 1) therapy received treatment after 3:00 PM.	Drug: PD-1/PD-L1 inhibitor monotherapy - 4 cycles after 3 PM; PD-1 (programmed cell death protein 1) or PD-L1 (programmed death-ligand 1) inhibitor monotherapy will be administered after 3 PM for 4 cycles.
Experimental: Cohort 2A: HNSCC received Anti- PD-1 start prior 12:00 PM; Patients with advanced or metastatic locally advanced, resectable HNSCC eligible for standard-of-care anti-PD-1 (programmed cell death protein 1) therapy received treatment before 12:00 PM.	Drug: PD-1 inhibitor monotherapy - 2 cycles before 12:00PM; PD-1 (programmed cell death protein 1) inhibitor monotherapy will be administered before 12:00PM for 2 cycles.
Experimental: Cohort 2B: HNSCC received Anti- PD-1 start after 3:00 PM; Patients with advanced or metastatic locally advanced, resectable HNSCC eligible for standard-of-care anti-PD-1 (programmed cell death protein 1) therapy received treatment after 3:00 PM.	Drug: PD-1 inhibitor monotherapy - 2 cycles after 3 PM; PD-1 (programmed cell death protein 1) inhibitor monotherapy will be administered after 3 PM for 2 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) - non-small cell lung cancer (NSCLC)	Progression free survival (PFS) will be measured as the time from the date of randomization to the earliest date of radiographic disease progression (PD), as determined by RECIST 1.1, or death from any cause in subjects with advanced or metastatic non-small cell lung cancer (NSCLC).	Up to 2 years
Major Pathologic Response (MPR) -head and neck squamous cell carcinoma (HNSCC).	Major Pathologic Response (MPR) is defined as participant with ≤10% viable tumor in resected tumor tissue in patients with resectable head and neck squamous cell carcinoma (HNSCC).	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS) - non-small cell lung cancer (NSCLC)	Overall survival (OS) is defined as the time from randomization to death from any cause in subjects with advanced or metastatic non-small cell lung cancer (NSCLC).	Up to 2 years
Objective Response Rate (ORR) - non-small cell lung cancer (NSCLC)	Objective Response Rate defined as the proportion of patients achieving a Complete Response (CR) or Partial Response (PR) as determined by RECIST 1.1 To determine if time of day of immune checkpoint inhibitor administration impacts treatment response in subjects with advanced or metastatic non-small cell lung cancer (NSCLC).	Up to 2 years
Timing of surgery	Timing of surgery is defined as the time from the last neoadjuvant dose to the date of surgery.	Up to 3 months

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Shetal A Patel, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2033
• Study Completion (Estimated): January 1, 2033

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: programmed death-ligand 1; programmed cell death protein 1
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms
• Other Study ID Numbers: LCCC2526-DCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No