Advanced Non-Small Cell Lung Cancer (NSCLC)Phase 1/2NCT07190027
Immunodynamics-Guided Optimization of Individualized Immunochemotherapy in Advanced Driver-Negative NSCLC: A Randomized Trial
A Phase 1/2 study testing Arm 1： Standard Synchronous Group, Arm 2：Fixed Delay Group and Arm 3： Individualized Delay Group in people with Advanced Non-Small Cell Lung Cancer (NSCLC), run by First Affiliated Hospital of Wenzhou Medical University.
Trial summary
The goal of this clinical trial is to evaluate whether individualized sequencing of immunotherapy and chemotherapy based on immune dynamics can improve treatment outcomes in adults with advanced non-small cell lung cancer (NSCLC) without driver gene mutations. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Non-Small Cell Lung Cancer (NSCLC)
- What is being tested?
- Arm 1： Standard Synchronous Group, Arm 2：Fixed Delay Group and Arm 3： Individualized Delay Group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 246 participants
- Where
- No sites listed yet
- Study dates
- Nov 2025to Nov 2028
- Phase
- Phase 1/2
- 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:
- Voluntarily agree to participate, sign the informed consent form (ICF), and be able to comply with the study procedures.
- Age ≥18 years and ≤75 years at enrollment, both male and female participants are eligible.
- Histologically or cytologically confirmed stage IV non-small cell lung cancer (NSCLC) based on the AJCC 8th edition; if mixed histology exists, classification must be based on the predominant histologic component. Presence of small-cell histology excludes eligibility.
- Negative for actionable driver mutations: no EGFR mutations, ALK rearrangements, or ROS1 fusions. For other targetable alterations (e.g., BRAF V600E, NTRK1/2/3 fusions, MET exon 14 skipping, RET rearrangements), patients are excluded if FDA- or NMPA-approved targeted therapies are available.
- Note: Genetic testing can be conducted locally or via a central laboratory. Pre-existing valid reports are acceptable.
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- Estimated life expectancy ≥3 months. At least one measurable lesion per RECIST v1.1 confirmed by IRC; irradiated lesions are not considered measurable unless unequivocal progression is demonstrated.
- ECOG performance status of 0 or 1. No prior systemic therapy for advanced/metastatic NSCLC, except adjuvant or neoadjuvant chemotherapy if the last dose was ≥6 months before recurrence.
- Adequate organ and bone marrow function within 14 days prior to randomization:
- ANC ≥ 1.5 × 10⁹/L Platelets ≥ 100 × 10⁹/L Hemoglobin ≥ 90 g/L Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula) Total bilirubin ≤ 1.5 × ULN (≤3 × ULN for Gilbert's syndrome) AST/ALT ≤ 2.5 × ULN (≤5 × ULN if liver metastases) INR and APTT ≤ 1.5 × ULN unless on therapeutic anticoagulation LVEF ≥ 50% by echocardiography or MUGA Female patients of childbearing potential must test negative for pregnancy within 14 days before enrollment and agree to use effective contraception from ICF signing until 180 days after the last dose. Male participants must also agree to effective contraception during the same period.
Who cannot join
- Participants meeting any of the following are excluded:
- Prior thoracic radiotherapy >30 Gy within 6 months before first dose. Palliative radiotherapy within 7 days before first dose. Requirement for concurrent anti-tumor therapy during the study. Uncontrolled or symptomatic pleural, pericardial, or peritoneal effusions requiring repeated drainage.
- Brainstem, leptomeningeal, spinal cord metastases, or cord compression.
- Active CNS metastases or carcinomatous meningitis. Treated, stable brain metastases are allowed if:
- Clinically stable ≥2 weeks, No evidence of progression, Off corticosteroids ≥3 days prior to treatment initiation. Previous treatment with immune checkpoint inhibitors (PD-1/PD-L1, CTLA-4, etc.), immune agonists, or cellular immunotherapies.
- Use of traditional Chinese medicines or immunomodulatory drugs with anti-cancer activity within 2 weeks before first dose.
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- Systemic corticosteroids (>10 mg prednisone equivalent/day) or other immunosuppressants within 2 weeks prior to first dose.
- Uncontrolled systemic infection, unexplained fever >38.5°C, or IV antibiotic use >7 days within 2 weeks prior to first dose.
- History of other malignancies within the past 5 years, except adequately treated cervical carcinoma in situ, basal/squamous cell skin cancer, localized thyroid papillary carcinoma, prostate cancer in remission, or DCIS after curative surgery.
- Active or history of autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial lung disease, uveitis, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, or hypothyroidism.
- Controlled hypothyroidism with hormone replacement is eligible. Vitiligo, alopecia, type 1 diabetes, resolved childhood asthma, or mild psoriasis without systemic therapy are allowed.
- Clinically significant pulmonary diseases: e.g., steroid-requiring pneumonitis, drug-induced pneumonitis, or moderate-to-severe COPD.
- Major surgery within 4 weeks prior to first dose or unresolved surgical wounds.
- Significant cardiovascular diseases, including:
- MI, unstable angina, stroke, or TIA within 6 months Arterial thromboembolism within 6 months DVT, PE, or severe thrombosis within 3 months Uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) Myocarditis or NYHA III-IV heart failure History of allogeneic HSCT or organ transplantation (except corneal).
- ≥ Grade 2 peripheral neuropathy per CTCAE v5.0. Active tuberculosis or suspected TB not ruled out. Positive HIV antibody; active syphilis or untreated positive non-treponemal antibody; uncontrolled HBV/HCV infection per protocol definition.
- Live vaccine administration within 30 days before first dose or planned during study.
- History of severe hypersensitivity to monoclonal antibodies, PD-1 agents, pemetrexed, carboplatin, or premedications.
- Concurrent participation in another interventional clinical trial or use of other investigational products/devices within 4 weeks prior to first dose.
- History of drug/alcohol abuse or uncontrolled psychiatric disorders interfering with compliance.
- Any other condition judged by the investigator as inappropriate for study participation.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Prospective Randomized Controlled Trial of Immunodynamics-Guided Optimization of Individualized Immunochemotherapy Infusion Timing in Driver Gene-Negative Advanced Non-Small Cell Lung Cancer
The goal of this clinical trial is to evaluate whether individualized sequencing of immunotherapy and chemotherapy based on immune dynamics can improve treatment outcomes in adults with advanced non-small cell lung cancer (NSCLC) without driver gene mutations. This study will also assess the safety and feasibility of different infusion strategies.
The main questions it aims to answer are:
Read more
Does optimizing the timing of PD-1 inhibitor infusion relative to chemotherapy improve the objective response rate (ORR)?
Does individualized infusion sequencing enhance progression-free survival (PFS) compared to standard or fixed-delay administration?
What safety concerns or immune-related adverse events occur with different infusion timing strategies?
Researchers will compare three treatment strategies:
Group A (Standard Concurrent Group): Immunotherapy and chemotherapy administered on the same day (D1).
Group B (Fixed Delay Group): Chemotherapy on D1, followed by PD-1 inhibitor infusion on Day 3.
Group C (Individualized Delay Group): Chemotherapy on D1, and PD-1 inhibitor infusion scheduled on D2-D6 based on daily immune monitoring.
Participants will:
Receive a PD-1 inhibitor (e.g., sintilimab, pembrolizumab, camrelizumab) combined with platinum-based chemotherapy.
Attend clinic visits for regular immune monitoring, imaging assessments, and safety checks during each treatment cycle.
Undergo blood tests to evaluate immune biomarkers (e.g., CD8⁺PD-1⁺ T cells, MDSC, Treg、IFN-γ、NLR、ALC、CRP) to guide individualized treatment decisions.
Read the detailed description
Detailed Description
This study is a prospective, randomized, open-label, multicenter exploratory clinical trial designed to evaluate the efficacy and safety of immunodynamics-guided optimization of chemoimmunotherapy scheduling in patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. The trial specifically investigates whether individualized scheduling of PD-1 inhibitor infusion, guided by dynamic immune monitoring, can improve antitumor activity compared with standard synchronous or fixed-delay administration.
Rationale and Background
For patients with metastatic NSCLC lacking EGFR, ALK, or other approved targetable alterations, chemoimmunotherapy has become the standard first-line treatment. However, clinical outcomes remain heterogeneous, and not all patients benefit equally. Preclinical and translational evidence suggests that the timing of immune checkpoint blockade relative to chemotherapy exposure may significantly influence immune response, tumor microenvironment remodeling, and overall treatment efficacy. Immunodynamics-the dynamic assessment of immune status during therapy-offers a novel approach to guide individualized administration of immunotherapy, potentially enhancing efficacy while maintaining safety.
Study Objectives
Primary Objective: To compare the objective response rate (ORR) among three treatment arms:
Arm A: Standard synchronous administration of chemotherapy and PD-1 inhibitor.
Arm B: Fixed-delay administration, with PD-1 inhibitor given three days after chemotherapy.
Arm C: Individualized-delay administration, where PD-1 inhibitor infusion timing (Day 2-6) is determined by peripheral blood immunodynamic markers.
Secondary Objectives: To evaluate progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), safety, and incidence of immune-related adverse events (irAEs).
Exploratory Objectives: To explore the relationship between immune scheduling and peripheral immune dynamics (CD8⁺PD-1⁺ T cells, myeloid-derived suppressor cells [MDSCs], Tregs, cytokines, etc.), as well as the predictive value of these markers for therapeutic outcomes.
Study Design
A total of 246 eligible patients with untreated metastatic, driver gene-negative NSCLC will be randomized in a 1:1:1 ratio into Arms A, B, and C (82 patients per arm). Treatment will consist of four cycles of chemoimmunotherapy followed by PD-1 inhibitor maintenance until disease progression, unacceptable toxicity, or a maximum of 2 years.
Arm A (Standard Synchronous): Chemotherapy and PD-1 inhibitor administered on Day 1 of each cycle.
Arm B (Fixed-Delay): Chemotherapy on Day 1; PD-1 inhibitor on Day 4.
Arm C (Individualized-Delay): Chemotherapy on Day 1; immune markers (CD8⁺PD-1⁺ T cells, MDSCs, Tregs, ± cytokines) measured on Days 2-5; PD-1 inhibitor administered when immunodynamic criteria are met, or on Day 6 as default.
Treatment cycles will repeat every 3 weeks. Imaging will be performed every 6 weeks during the first 48 weeks, then every 9 weeks, using RECIST v1.1 criteria. Patients will be followed for safety and survival after treatment discontinuation.
Endpoints
Primary Endpoint: Objective response rate (ORR) assessed by independent radiologic review committee (IRC).
Secondary Endpoints: PFS, OS, DCR, DOR, safety, incidence and severity of irAEs and treatment-related adverse events.
Exploratory Endpoints: Dynamic immune monitoring parameters, association between immune recovery patterns and clinical outcomes, correlation of PD-L1 expression and immune biomarkers, and exploratory ctDNA analyses if feasible.
Statistical Considerations
The study is powered to detect clinically meaningful improvements in ORR. Stratified CMH tests will be used for ORR comparisons. Kaplan-Meier methods and Cox proportional hazards models will be applied for time-to-event endpoints (PFS, OS, DOR). Exploratory analyses will examine associations between immunodynamic markers and outcomes, and predictive biomarker models will be developed. Safety analyses will summarize adverse events by frequency, grade, and relatedness.
Significance
This trial represents the first randomized study to prospectively test immunodynamics-guided optimization of immunochemotherapy scheduling in NSCLC. By integrating real-time immune monitoring into treatment decision-making, the study aims to generate evidence for precision timing of PD-1 inhibitor administration, potentially enhancing treatment efficacy and safety. Results from this study may inform future clinical practice and contribute to individualized immunotherapy strategies in lung cancer and beyond.
- Being tested
- Arm 1： Standard Synchronous Group, Arm 2：Fixed Delay Group, Arm 3： Individualized Delay Group
- Keywords
- Non-Small Cell Lung Cancer (NSCLC), Driver Gene-Negative NSCLC, Immunochemotherapy Sequencing, Individualized Infusion Timing, Immune Dynamics
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1： Standard Synchronous GroupDrug
Also called Concurrent PD-1 + Chemotherapy
Arm 1: Concurrent PD-1 + Chemotherapy (Standard Synchronous Group) Participants in this group will receive PD-1 inhibitor and chemotherapy on the same day (D1) during each treatment cycle.
Arm 2：Fixed Delay GroupDrug
Also called PD-1 Delayed Administration on D3 (Fixed Delay Group) Participants in this group will receive chemotherapy on D1 and then receive the PD-1 inhibitor on D3 of each cycle.
Fixed Delay Arm Delayed PD-1 + Chemo PD-1 inhibitor (e.g., Sintilimab/Keytruda/Tislelizumab/Camrelizumab/Toripalimab/Nivolumab/Atezolizumab/Sugemalimab) Immune checkpoint inhibitor + Chemo (Day 3)
Arm 3： Individualized Delay GroupDrug
Arm 3: Individualized PD-1 Timing Based on Immune Window Score (IWS) (Individualized Group) Participants in this group will receive chemotherapy on D1 and undergo daily immune monitoring (CD8⁺PD-1⁺ T cells, Treg, IFN-γ, NLR, ALC, CRP).
Based on the immune window score (IWS):
If IWS ≥ 2, PD-1 inhibitor will be administered the same day. If IWS = 1-1.5, dosing may be delayed to D3-D5 depending on immune recovery. If IWS remains 0 by D5, PD-1 inhibitor will be administered on D6 as fallback.
| Study group | Role | What they receive |
|---|---|---|
| Arm 2: Fixed Delay Group | Experimental | Patients receive standard chemotherapy on Day 1 of each 21-day cycle. The PD-1 inhibitor is administered with a fixed delay, on Day 4 (3 days after chemotherapy). Combination treatment is given for 4 cycles, followed by PD-1 inhibitor maintenance until disease progression, unacceptable toxicity Receives: Drug: Arm 2：Fixed Delay Group |
| Arm 1: Standard Synchronous Group | Experimental | Patients receive standard chemotherapy and PD-1 inhibitor concurrently on Day 1 of each 21-day cycle. After 4 cycles of combination therapy, patients continue PD-1 inhibitor maintenance until progression Receives: Drug: Arm 1： Standard Synchronous Group |
| Arm 3: Individualized Delay Group | Experimental | Patients receive chemotherapy on Day 1 of each 21-day cycle. From Day 2 to Day 5, peripheral blood immunodynamic markers (e.g., CD8⁺PD-1⁺ T cells, MDSCs, Tregs, cytokines) are monitored daily. The PD-1 inhibitor is administered at the optimal time when predefined immunodynamic criteria are met, or on Day 6 if criteria are not met. After 4 cycles of combination therapy, patients continue PD-1 inhibitor maintenance until progression Receives: Drug: Arm 3： Individualized Delay Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The proportion of participants who achieve a complete response (CR) or partial response (PR) based on RECIST v1.1 criteria, as assessed by investigators. Imaging assessments will be performed every 6-8 weeks during treatment, and responses will be confirmed at least 4 weeks after initial documentation.
Measured: From baseline until disease progression, death, or completion of treatment, whichever occurs first, up to approximately 36 months.
Secondary outcomes (4)
PFS
PFS is defined as the time from the start of treatment until disease progression as assessed by RECIST v1.1 criteria or death from any cause, whichever occurs first. Imaging assessments will be performed every 6-8 weeks.
Measured: From baseline until documented disease progression or death, up to approximately 36 months.
Overall Survival (OS)
OS is defined as the time from the start of treatment until death from any cause. Participants alive at the time of analysis will be censored at the last date known to be alive.
Measured: From baseline until death from any cause, up to approximately 48 months.
Incidence of Immune-Related Adverse Events (irAEs)
The percentage of participants experiencing any grade immune-related adverse events, as defined by CTCAE v5.0, including but not limited to dermatitis, colitis, pneumonitis, hepatitis, and endocrinopathies.
Measured: From baseline through 90 days after the last dose of study treatment, up to approximately 36 months.
Incidence of Treatment-Related Adverse Events (TRAEs)
The percentage of participants experiencing any grade treatment-related adverse events, assessed by investigators and graded according to CTCAE v5.0.
Measured: From baseline through 90 days after the last dose of study treatment, up to approximately 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2025
- Study startNov 2025 (estimated)
- Primary completionNov 2025 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 246 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Wenzhou Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liang bin, First Affiliated Hospital of Wenzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07190027
- Sponsor's protocol ID
- KY2025-309
- Status last verified
- Sep 2025
- First submitted
- 10 Sep 2025
- Last updated
- 24 Sep 2025
- Results posted
- No
- 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 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Randomized Controlled Trial of Immunodynamics-Guided Optimization of Individualized Immunochemotherapy Infusion Timing in Driver Gene-Negative Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT07190027
- Acronym / sponsor ID
- KY2025-309
- Keywords
- Non-Small Cell Lung Cancer (NSCLC), Driver Gene-Negative NSCLC, Immunochemotherapy Sequencing, Individualized Infusion Timing, Immune Dynamics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 246 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Wenzhou Medical UniversityUniversity, hospital or other
- Study start
- Nov 2025 (estimated)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 24 Sep 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.
The goal of this clinical trial is to evaluate whether individualized sequencing of immunotherapy and chemotherapy based on immune dynamics can improve treatment outcomes in adults with advanced non-small cell lung cancer (NSCLC) without driver gene mutations. This study will also assess the safety and feasibility of different infusion strategies.
The main questions it aims to answer are:
Does optimizing the timing of PD-1 inhibitor infusion relative to chemotherapy improve the objective response rate (ORR)?
Does individualized infusion sequencing enhance progression-free survival (PFS) compared to standard or fixed-delay administration?
What safety concerns or immune-related adverse events occur with different infusion timing strategies?
Researchers will compare three treatment strategies:
Group A (Standard Concurrent Group): Immunotherapy and chemotherapy administered on the same day (D1).
Group B (Fixed Delay Group): Chemotherapy on D1, followed by PD-1 inhibitor infusion on Day 3.
Group C (Individualized Delay Group): Chemotherapy on D1, and PD-1 inhibitor infusion scheduled on D2-D6 based on daily immune monitoring.
Participants will:
Receive a PD-1 inhibitor (e.g., sintilimab, pembrolizumab, camrelizumab) combined with platinum-based chemotherapy.
Attend clinic visits for regular immune monitoring, imaging assessments, and safety checks during each treatment cycle.
Undergo blood tests to evaluate immune biomarkers (e.g., CD8⁺PD-1⁺ T cells, MDSC, Treg、IFN-γ、NLR、ALC、CRP) to guide individualized treatment decisions.
Detailed description
Detailed Description
This study is a prospective, randomized, open-label, multicenter exploratory clinical trial designed to evaluate the efficacy and safety of immunodynamics-guided optimization of chemoimmunotherapy scheduling in patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. The trial specifically investigates whether individualized scheduling of PD-1 inhibitor infusion, guided by dynamic immune monitoring, can improve antitumor activity compared with standard synchronous or fixed-delay administration.
Rationale and Background
For patients with metastatic NSCLC lacking EGFR, ALK, or other approved targetable alterations, chemoimmunotherapy has become the standard first-line treatment. However, clinical outcomes remain heterogeneous, and not all patients benefit equally. Preclinical and translational evidence suggests that the timing of immune checkpoint blockade relative to chemotherapy exposure may significantly influence immune response, tumor microenvironment remodeling, and overall treatment efficacy. Immunodynamics-the dynamic assessment of immune status during therapy-offers a novel approach to guide individualized administration of immunotherapy, potentially enhancing efficacy while maintaining safety.
Study Objectives
Primary Objective: To compare the objective response rate (ORR) among three treatment arms:
Arm A: Standard synchronous administration of chemotherapy and PD-1 inhibitor.
Arm B: Fixed-delay administration, with PD-1 inhibitor given three days after chemotherapy.
Arm C: Individualized-delay administration, where PD-1 inhibitor infusion timing (Day 2-6) is determined by peripheral blood immunodynamic markers.
Secondary Objectives: To evaluate progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), safety, and incidence of immune-related adverse events (irAEs).
Exploratory Objectives: To explore the relationship between immune scheduling and peripheral immune dynamics (CD8⁺PD-1⁺ T cells, myeloid-derived suppressor cells [MDSCs], Tregs, cytokines, etc.), as well as the predictive value of these markers for therapeutic outcomes.
Study Design
A total of 246 eligible patients with untreated metastatic, driver gene-negative NSCLC will be randomized in a 1:1:1 ratio into Arms A, B, and C (82 patients per arm). Treatment will consist of four cycles of chemoimmunotherapy followed by PD-1 inhibitor maintenance until disease progression, unacceptable toxicity, or a maximum of 2 years.
Arm A (Standard Synchronous): Chemotherapy and PD-1 inhibitor administered on Day 1 of each cycle.
Arm B (Fixed-Delay): Chemotherapy on Day 1; PD-1 inhibitor on Day 4.
Arm C (Individualized-Delay): Chemotherapy on Day 1; immune markers (CD8⁺PD-1⁺ T cells, MDSCs, Tregs, ± cytokines) measured on Days 2-5; PD-1 inhibitor administered when immunodynamic criteria are met, or on Day 6 as default.
Treatment cycles will repeat every 3 weeks. Imaging will be performed every 6 weeks during the first 48 weeks, then every 9 weeks, using RECIST v1.1 criteria. Patients will be followed for safety and survival after treatment discontinuation.
Endpoints
Primary Endpoint: Objective response rate (ORR) assessed by independent radiologic review committee (IRC).
Secondary Endpoints: PFS, OS, DCR, DOR, safety, incidence and severity of irAEs and treatment-related adverse events.
Exploratory Endpoints: Dynamic immune monitoring parameters, association between immune recovery patterns and clinical outcomes, correlation of PD-L1 expression and immune biomarkers, and exploratory ctDNA analyses if feasible.
Statistical Considerations
The study is powered to detect clinically meaningful improvements in ORR. Stratified CMH tests will be used for ORR comparisons. Kaplan-Meier methods and Cox proportional hazards models will be applied for time-to-event endpoints (PFS, OS, DOR). Exploratory analyses will examine associations between immunodynamic markers and outcomes, and predictive biomarker models will be developed. Safety analyses will summarize adverse events by frequency, grade, and relatedness.
Significance
This trial represents the first randomized study to prospectively test immunodynamics-guided optimization of immunochemotherapy scheduling in NSCLC. By integrating real-time immune monitoring into treatment decision-making, the study aims to generate evidence for precision timing of PD-1 inhibitor administration, potentially enhancing treatment efficacy and safety. Results from this study may inform future clinical practice and contribute to individualized immunotherapy strategies in lung cancer and beyond.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 2: Fixed Delay Group | Experimental | Drug: Arm 2：Fixed Delay GroupPatients receive standard chemotherapy on Day 1 of each 21-day cycle. The PD-1 inhibitor is administered with a fixed delay, on Day 4 (3 days after chemotherapy). Combination treatment is given for 4 cycles, followed by PD-1 inhibitor maintenance until disease progression, unacceptable toxicity |
| Arm 1: Standard Synchronous Group | Experimental | Drug: Arm 1： Standard Synchronous GroupPatients receive standard chemotherapy and PD-1 inhibitor concurrently on Day 1 of each 21-day cycle. After 4 cycles of combination therapy, patients continue PD-1 inhibitor maintenance until progression |
| Arm 3: Individualized Delay Group | Experimental | Drug: Arm 3： Individualized Delay GroupPatients receive chemotherapy on Day 1 of each 21-day cycle. From Day 2 to Day 5, peripheral blood immunodynamic markers (e.g., CD8⁺PD-1⁺ T cells, MDSCs, Tregs, cytokines) are monitored daily. The PD-1 inhibitor is administered at the optimal time when predefined immunodynamic criteria are met, or on Day 6 if criteria are not met. After 4 cycles of combination therapy, patients continue PD-1 inhibitor maintenance until progression |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Voluntarily agree to participate, sign the informed consent form (ICF), and be able to comply with the study procedures.
- Age ≥18 years and ≤75 years at enrollment, both male and female participants are eligible.
- Histologically or cytologically confirmed stage IV non-small cell lung cancer (NSCLC) based on the AJCC 8th edition; if mixed histology exists, classification must be based on the predominant histologic component. Presence of small-cell histology excludes eligibility.
- Negative for actionable driver mutations: no EGFR mutations, ALK rearrangements, or ROS1 fusions. For other targetable alterations (e.g., BRAF V600E, NTRK1/2/3 fusions, MET exon 14 skipping, RET rearrangements), patients are excluded if FDA- or NMPA-approved targeted therapies are available.
- Note: Genetic testing can be conducted locally or via a central laboratory. Pre-existing valid reports are acceptable.
Key exclusion criteria (21 listed)
- Prior thoracic radiotherapy >30 Gy within 6 months before first dose. Palliative radiotherapy within 7 days before first dose. Requirement for concurrent anti-tumor therapy during the study. Uncontrolled or symptomatic pleural, pericardial, or peritoneal effusions requiring repeated drainage.
- Brainstem, leptomeningeal, spinal cord metastases, or cord compression.
- Active CNS metastases or carcinomatous meningitis. Treated, stable brain metastases are allowed if:
- Clinically stable ≥2 weeks, No evidence of progression, Off corticosteroids ≥3 days prior to treatment initiation. Previous treatment with immune checkpoint inhibitors (PD-1/PD-L1, CTLA-4, etc.), immune agonists, or cellular immunotherapies.
- Use of traditional Chinese medicines or immunomodulatory drugs with anti-cancer activity within 2 weeks before first dose.
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 |
|---|---|---|
| Arm 1： Standard Synchronous GroupAlso: Concurrent PD-1 + ChemotherapyArm 1: Concurrent PD-1 + Chemotherapy (Standard Synchronous Group) Participants in this group will receive PD-1 inhibitor and chemotherapy on the same day (D1) during each treatment cycle. | Drug | Arm 1: Standard Synchronous Group |
| Arm 2：Fixed Delay GroupAlso: PD-1 Delayed Administration on D3 (Fixed Delay Group) Participants in this group will receive chemotherapy on D1 and then receive the PD-1 inhibitor on D3 of each cycle.Fixed Delay Arm Delayed PD-1 + Chemo PD-1 inhibitor (e.g., Sintilimab/Keytruda/Tislelizumab/Camrelizumab/Toripalimab/Nivolumab/Atezolizumab/Sugemalimab) Immune checkpoint inhibitor + Chemo (Day 3) | Drug | Arm 2: Fixed Delay Group |
| Arm 3： Individualized Delay GroupArm 3: Individualized PD-1 Timing Based on Immune Window Score (IWS) (Individualized Group) Participants in this group will receive chemotherapy on D1 and undergo daily immune monitoring (CD8⁺PD-1⁺ T cells, Treg, IFN-γ, NLR, ALC, CRP). Based on the immune window score (IWS): If IWS ≥ 2, PD-1 inhibitor will be administered the same day. If IWS = 1-1.5, dosing may be delayed to D3-D5 depending on immune recovery. If IWS remains 0 by D5, PD-1 inhibitor will be administered on D6 as fallback. | Drug | Arm 3: Individualized Delay Group |
Primary outcome
Objective Response Rate (ORR)
Time frame: From baseline until disease progression, death, or completion of treatment, whichever occurs first, up to approximately 36 months.
The proportion of participants who achieve a complete response (CR) or partial response (PR) based on RECIST v1.1 criteria, as assessed by investigators. Imaging assessments will be performed every 6-8 weeks during treatment, and responses will be confirmed at least 4 weeks after initial documentation.
4 secondary outcomes
PFS
Time frame: From baseline until documented disease progression or death, up to approximately 36 months.
Overall Survival (OS)
Time frame: From baseline until death from any cause, up to approximately 48 months.
Incidence of Immune-Related Adverse Events (irAEs)
Time frame: From baseline through 90 days after the last dose of study treatment, up to approximately 36 months.
Incidence of Treatment-Related Adverse Events (TRAEs)
Time frame: From baseline through 90 days after the last dose of study treatment, up to approximately 36 months.
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 24 Sep 2025.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Arm 1： Standard Synchronous Group, Arm 2：Fixed Delay Group and Arm 3： Individualized Delay Group in people with Advanced Non-Small Cell Lung Cancer (NSCLC), run by First Affiliated Hospital of Wenzhou Medical University.
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 10 inclusion and 21 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: opening soon, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 xiaona xie (86+13758469563, xiexiaona@wmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: From baseline until disease progression, death, or completion of treatment, whichever occurs first, up to approximately 36 months.). 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 24 Sep 2025.