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

NCT07251582 | Recruiting Phase 3 DMC

• 1 other identifier: LungTime-C02
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

NSCLC; Time of day; neoadjuvant treatment

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) rate

  Proportion of patients achieving pathological complete response (no viable tumor cells in resected primary tumor and sampled regional lymph nodes) assessed on surgical specimen after completion of neoadjuvant therapy and surgery.

  At the time of surgery, approximately 6-9 weeks after randomization

Secondary Outcomes (2)

• Event Free Survival (EFS)

  From date of randomization to event occurrence (disease progression, recurrence, or death), assessed up to 36 months

• Major Pathological Response (MPR) rate

  At the time of surgery, approximately 6-9 weeks after randomization

Study Arms (2)

Morning infusion group

EXPERIMENTAL

• 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.

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

Afternoon infusion group

ACTIVE COMPARATOR

• 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.

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

Interventions

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

Afternoon infusion group; Morning infusion group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Age ≥18 and ≤75 years at the time of enrollment.
• Histologically or cytologically confirmed diagnosis of resectable stage II to III non-small cell lung cancer (NSCLC).
• Deemed suitable for neoadjuvant immunotherapy combined with platinum-based chemotherapy and subsequent surgical resection based on multidisciplinary team (MDT) assessment.
• ECOG Performance Status of 0 or 1.
• No prior systemic antitumor therapy for the current NSCLC diagnosis.
• Adequate bone marrow, hepatic, renal, and cardiac function based on local laboratory standards.
• Willing and able to comply with scheduled visits, treatment plans, and other study procedures.
• Signed informed consent prior to participation.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded:
• Presence of EGFR-sensitive mutations (e.g., exon 19del, L858R) or ALK/ROS1 rearrangements.
• Presence of uncontrolled or symptomatic brain metastases.
• 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.
• History of prior systemic therapy (immunotherapy, chemotherapy, or targeted therapy) for lung cancer.
• Known severe allergic reactions to PD-1 or PD-L1 inhibitors (Grade ≥3 by CTCAE).
• Active autoimmune disease requiring systemic immunosuppression.
• Active infections, including active HBV, HCV, or HIV infection.
• Pregnant or breastfeeding women.
• Any comorbid condition or uncontrolled illness that, in the opinion of the investigator, may interfere with study participation or pose unacceptable risk.

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (2)

Hunna Cancer Hospital, Clinical Trails Center

Changsha, Hunan, 410013, China

RECRUITING

Hunan Cancer hospital

Changsha, Hunan, China

RECRUITING

MeSH Terms

Interventions

toripalimab; pembrolizumab; Platinum Compounds

Intervention Hierarchy (Ancestors)

Inorganic Chemicals

Central Study Contacts

Yongchang Zhang, professor

CONTACT

+0086 13873123436; zhanglei1152@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DR

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: November 26, 2025
• Study Start: December 7, 2025
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): May 31, 2029
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)