Resectable Stage II-III Non-Small Cell Lung Cancer (NSCLC)
Conditions
Keywords
NSCLC, Time of day, neoadjuvant treatment
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.
Interventions
OTHERTime 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.
Sponsors
Hunan Province Tumor Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) rate | At the time of surgery, approximately 6-9 weeks after randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival (EFS) | From date of randomization to event occurrence (disease progression, recurrence, or death), assessed up to 36 months | Time from randomization to disease progression that precludes surgery, recurrence, or death from any cause, whichever occurs first. |
| Major Pathological Response (MPR) rate | At the time of surgery, approximately 6-9 weeks after randomization | Proportion of patients with ≤10% viable tumor cells in the resected primary tumor specimen. |
Countries
China
Contacts
CONTACTYongchang Zhang, professor
Outcome results
None listed