Infusion timing and pathologic response to neoadjuvant immunotherapy in resectable NSCLC

A Prospective Study on the Effect of Infusion Timing of Immune Checkpoint Inhibitors on Pathologic Response in Patients With Resectable Stage II-III Non-Small Cell Lung Cancer Undergoing Neoadjuvant Therapy

This trial will test whether getting immunotherapy infusions in the morning versus the afternoon changes tumor response in people with resectable stage II–III non-small cell lung cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 156 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hunan Province Tumor Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, toripalimab, pembrolizumab
• Locations: 2 sites (Changsha, Hunan and 1 other locations)
• Trial ID: NCT07251582 on ClinicalTrials.gov

What this trial studies

This randomized phase 3 study assigns patients with resectable stage II–III NSCLC to receive all immune checkpoint inhibitor infusions either in a morning window (08:00–11:00) or an afternoon window (15:00–18:00) alongside standard platinum-based neoadjuvant chemotherapy. The primary endpoint is pathological complete response (pCR) after surgery, with secondary endpoints including major pathological response (MPR) and event-free survival (EFS). Independent imaging and pathology review will be used for endpoint assessment. The trial is designed to provide prospective evidence on whether circadian timing of ICI administration affects neoadjuvant treatment efficacy.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed resectable stage II–III NSCLC, ECOG 0–1, no prior systemic therapy, and who are candidates for neoadjuvant ICI plus platinum chemotherapy and surgery are eligible.

Not a fit: Patients with EGFR-sensitive mutations or ALK/ROS1 rearrangements, unresectable disease, prior systemic therapy for this diagnosis, or poor performance status are unlikely to be eligible or benefit from the timing comparison.

Why it matters

Potential benefit: If morning versus afternoon infusion timing improves pathological response, patients could achieve higher pCR rates without changing drugs or increasing toxicity.

How similar studies have performed: Retrospective analyses in multiple cancer types have suggested better outcomes with morning ICI infusions, but prospective randomized evidence—especially in the neoadjuvant resectable NSCLC setting—is not yet available.

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.

Where this trial is running

Changsha, Hunan and 1 other locations

• Hunna Cancer Hospital, Clinical Trails Center — Changsha, Hunan, China (Recruiting)
• Hunan Cancer hospital — Changsha, Hunan, China (Recruiting)

Study contacts

• Study coordinator: Yongchang Zhang, professor

Conditions Resectable Stage II-III Non-Small Cell Lung Cancer; NSCLC; Time of day; neoadjuvant treatment