Resectable Stage II-III Non-Small Cell Lung Cancer (NSCLC)Phase 3LungTime-C02NCT07251582
Effect of Infusion Timing on Pathologic Response to Neoadjuvant Immunotherapy in Resectable Non-Small Cell Lung Cancer
A Phase 3 study testing Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy in people with Resectable Stage II-III Non-Small Cell Lung Cancer (NSCLC), run by Hunan Province Tumor Hospital at 2 sites in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Resectable Stage II-III Non-Small Cell Lung Cancer (NSCLC)
- What is being tested?
- Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 2 sitesChina
- Study dates
- 12 Aug 2026to 31 May 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Hunna Cancer Hospital, Clinical Trails Center
Changsha, Hunan, 410013
Yongchang Zhang, MD, +13873123436, zhangyongchang@csu.edu.cn
Liang Zeng, MD, +8673189762650, 530490930@qq.com
- Recruiting
Hunan Cancer hospital
Changsha, Hunan
Yongchang Zhang, MD, +86 13873123436, zhangyongchang@csu.edu.cn
About this study
Official title: 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 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.
Read the 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.
- Being tested
- Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy
- Keywords
- NSCLC, Time of day, neoadjuvant treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the time of surgery, approximately 6-9 weeks after randomization
Secondary outcomes (2)
Event Free Survival (EFS)
Time from randomization to disease progression that precludes surgery, recurrence, or death from any cause, whichever occurs first.
Measured: From date of randomization to event occurrence (disease progression, recurrence, or death), assessed up to 36 months
Major Pathological Response (MPR) rate
Proportion of patients with ≤10% viable tumor cells in the resected primary tumor specimen.
Measured: At the time of surgery, approximately 6-9 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2025
- Study start12 Aug 2026 (estimated)
- Primary completion31 Oct 2028 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Resectable Stage II-III Non-Small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 186 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hunan Province Tumor Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yongchang Zhang, Hunan Province Tumor Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07251582
- Sponsor's protocol ID
- LungTime-C02
- Acronym
- LungTime-C02
- Status last verified
- Nov 2025
- First submitted
- 16 Nov 2025
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07251582
- Acronym / sponsor ID
- LungTime-C02 / LungTime-C02
- Keywords
- NSCLC, Time of day, neoadjuvant treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 186 participants (estimated)
- Lead sponsor
- Hunan Province Tumor HospitalUniversity, hospital or other
- Study start
- 12 Aug 2026 (estimated)
- Primary completion
- 31 Oct 2028 (estimated)
- Study completion
- 31 May 2029 (estimated)
- First posted
- 26 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morning infusion group | Experimental | Other: Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy• 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. |
| Afternoon infusion group | Active comparator | Other: Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy• 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapyPatients 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. | Other | Afternoon infusion group, Morning infusion group |
Primary outcome
Pathological Complete Response (pCR) rate
Time frame: 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.
2 secondary outcomes
Event Free Survival (EFS)
Time frame: From date of randomization to event occurrence (disease progression, recurrence, or death), assessed up to 36 months
Major Pathological Response (MPR) rate
Time frame: At the time of surgery, approximately 6-9 weeks after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Time of Day-based Assignment for Infusion of Immune Checkpoint Inhibitor (e.g., toripalimab, or pembrolizumab) + platinum-based chemotherapy in people with Resectable Stage II-III Non-Small Cell Lung Cancer (NSCLC), run by Hunan Province Tumor Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yongchang Zhang, professor (+0086 13873123436, zhanglei1152@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological Complete Response (pCR) rate (time frame: At the time of surgery, approximately 6-9 weeks after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.