Effect of Infusion Timing on Pathologic Response to Neoadjuvant Immunotherapy in Resectable Non-Small Cell Lung Cancer

NCT ID: NCT07251582

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-07
• Study Completion Date: 2029-05-31

Brief Summary

This prospective study aims to investigate whether the time of day when immune checkpoint inhibitors (ICIs) are administered affects the efficacy of neoadjuvant immunotherapy in patients with resectable stage II-III non-small cell lung cancer (NSCLC). Eligible patients will receive standard-of-care neoadjuvant ICI plus platinum-based chemotherapy and be randomly assigned to either a morning infusion group (08:00-11:00) or an afternoon infusion group (15:00-18:00). The primary objective is to compare the pathological complete response (pCR) rates between groups. Secondary outcomes include major pathological response (MPR) and event-free survival (EFS). The study will include independent imaging and pathology review for endpoint assessment.

Detailed Description

Emerging evidence suggests that the efficacy of immune checkpoint inhibitors (ICIs) may be influenced by the circadian timing of drug administration. Retrospective studies in multiple cancer types have indicated that morning infusion of ICIs might be associated with improved clinical outcomes compared to afternoon infusion. However, no prospective study has evaluated this phenomenon in the setting of neoadjuvant therapy for resectable non-small cell lung cancer (NSCLC).

This prospective, randomized, parallel-group study aims to assess whether the time of day of ICI infusion (morning vs. afternoon) affects the pathological response to neoadjuvant immunotherapy in patients with stage II-III resectable NSCLC.

Eligible patients will receive standard-of-care neoadjuvant treatment, consisting of an immune checkpoint inhibitor (e.g., toripalimab, or pembrolizumab) combined with platinum-based chemotherapy. Patients will be randomly assigned (1:1) to receive all ICI infusions during either the morning window (08:00-11:00) or the afternoon window (15:00-18:00), throughout the neoadjuvant treatment period.

The primary endpoint is the pathological complete response (pCR) rate after neoadjuvant therapy and surgery. Secondary endpoints include major pathological response (MPR), event-free survival (EFS).The study will include independent imaging and pathology review for endpoint assessment.

This study aims to provide prospective evidence on the role of infusion timing in optimizing immunotherapy efficacy. If successful, this approach could offer a simple, cost-effective, and non-invasive strategy to improve outcomes for patients undergoing neoadjuvant immunotherapy.

Conditions

Resectable Stage II-III Non-Small Cell Lung Cancer (NSCLC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Afternoon infusion group

• Intervention / treatment:

• Same systemic regimen as Arm 1, but all ICI infusions administered in the afternoon window (15:00-18:00).
• Chemotherapy, number of cycles (4), and surgical decision follow the same rules as Arm 1.
• Supportive care per routine practice.

Group Type: ACTIVE_COMPARATOR

Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy

Intervention Type: OTHER

Patients will be randomly assigned (1:1) to receive all ICI infusions during either the morning window (08:00-11:00) or the afternoon window (15:00-18:00), throughout the neoadjuvant treatment period.

Morning infusion group

• Intervention / treatment:

• Immune checkpoint inhibitor (one of approved PD 1 agents per investigator choice; e.g., toripalimab / pembrolizumab) administered in the morning window (08:00-11:00) for all ICI infusions during neoadjuvant treatment.
• Combined with platinum based chemotherapy per institutional standard (examples: nab paclitaxel 260 mg/m² IV Day 1 Q3W + carboplatin AUC 5 IV Day 1 Q3W; or paclitaxel/cisplatin regimens per local practice).
• Neoadjuvant treatment cycles: 4 cycles as per treating physician and local guideline; surgery scheduled after assessment.
• Supportive care per routine practice.

Group Type: EXPERIMENTAL

Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy

Intervention Type: OTHER

Patients will be randomly assigned (1:1) to receive all ICI infusions during either the morning window (08:00-11:00) or the afternoon window (15:00-18:00), throughout the neoadjuvant treatment period.

Interventions

Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy

Patients will be randomly assigned (1:1) to receive all ICI infusions during either the morning window (08:00-11:00) or the afternoon window (15:00-18:00), throughout the neoadjuvant treatment period.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Participants must meet all of the following criteria:

1. Age ≥18 and ≤75 years at the time of enrollment.

2. Histologically or cytologically confirmed diagnosis of resectable stage II to III non-small cell lung cancer (NSCLC).

3. Deemed suitable for neoadjuvant immunotherapy combined with platinum-based chemotherapy and subsequent surgical resection based on multidisciplinary team (MDT) assessment.

4. ECOG Performance Status of 0 or 1.

5. No prior systemic antitumor therapy for the current NSCLC diagnosis.

6. Adequate bone marrow, hepatic, renal, and cardiac function based on local laboratory standards.

7. Willing and able to comply with scheduled visits, treatment plans, and other study procedures.

8. Signed informed consent prior to participation.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded:

1. Presence of EGFR-sensitive mutations (e.g., exon 19del, L858R) or ALK/ROS1 rearrangements.

2. Presence of uncontrolled or symptomatic brain metastases.

3. History of any other malignancy within 3 years prior to enrollment, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or cervical carcinoma in situ.

4. History of prior systemic therapy (immunotherapy, chemotherapy, or targeted therapy) for lung cancer.

5. Known severe allergic reactions to PD-1 or PD-L1 inhibitors (Grade ≥3 by CTCAE).

6. Active autoimmune disease requiring systemic immunosuppression.

7. Active infections, including active HBV, HCV, or HIV infection.

8. Pregnant or breastfeeding women.

9. Any comorbid condition or uncontrolled illness that, in the opinion of the investigator, may interfere with study participation or pose unacceptable risk.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hunan Province Tumor Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yongchang Zhang

DR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hunna Cancer Hospital, Clinical Trails Center

Changsha, Hunan, China

Site Status: RECRUITING

Hunan Cancer hospital

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yongchang Zhang, professor

Role: CONTACT

zhanglei1152@126.com

+0086 13873123436

Facility Contacts

Yongchang Zhang, MD

Role: primary

zhangyongchang@csu.edu.cn

+13873123436

Liang Zeng, MD

Role: backup

530490930@qq.com

+8673189762650

Yongchang Zhang, MD

Role: primary

zhangyongchang@csu.edu.cn

+86 13873123436

Other Identifiers

LungTime-C02

Identifier Type: -

Identifier Source: org_study_id