Neoadjuvant/Adjuvant Pembrolizumab Plus Chemotherapy

Study Overview
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Brief Summary
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A phase II, single-arm, open-label study evaluating feasibility, safety and efficacy of combined chemotherapy and pembrolizumab as neoadjuvant/adjuvant therapy in stage IIa-IIIB NSCLC adult patients followed by adjuvant PD-(L)1 inhibitor treatment for up to 1 year

Detailed Description
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Two to four cycles of neoadjuvant chemotherapy in combination with pembrolizumab will be administered before surgery, followed by another one to two cycles of chemotherapy plus pembrolizumab after surgery (4 cycles neoadjuvant/adjuvant chemotherapy in total ) then use pembrolizumab monotherapy for up to 1 year.

Official Title
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A Prospective, Single-arm PhaseⅡTrial of Neoadjuvant/Adjuvant Pembrolizumab Plus Platinum-doublet Chemotherapy (Chemo) in IIa-IIIb NSCLC

Conditions
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Non Small Cell Lung Cancer, Neoadjuvant Therapy, Immune Checkpoint Inhibitor

Intervention / Treatment
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* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary non-small cell lung cancer (NSCLC) confirmed by cytology or histology Stage IIa to selected IIIb ( t1-4, n0-2 ) NSCLC according to the TNM stage (8th Edition) of IASLC, which is considered to be resectable; At least one evaluable focus judged according to RECIST 1.1 standard (on spiral CT, the longest diameter of tumor should be at least 10 mm, the shortest diameter of metastasis lymphnode should be at least 20 mm) ECOG PS 0 or 1 Adequate tumor samples available for gene detection (EGFR/ALK /ros1) with non-squamous and specimens for PD-L1 immunohistochemistry (IHC) in all the subjects. Male or female, ≥ 18 years old Adequate blood function: absolute neutrophil count (ANC) ≥ 2 × 109 / L, platelet count ≥ 100 × 109 / L and hemoglobin 110 ≥ 9 g / dl Adequate liver function: total bilirubin ≤ upper limit of normal value (ULN); AST and alt ≤ upper limit of normal value (ULN); alkaline phosphatase ≤ upper limit of normal value (ULN) Adequate renal function: serum creatinine ≤ upper limit of normal value (ULN) or calculated creatinine clearance ≥ 60ml / min No history of using anti-tumor drug treatment before For patients who have had previous surgery, it is required that more than 4 weeks have passed since the start of study treatment, and the patients have recovered Sign the informed consent form (the informed consent form needs to be approved by the independent ethics committee, and the informed consent of the patient should be obtained before starting any substantive trial procedure) Exclusion Criteria: Carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene or other known targetable driver mutations. Active, known or suspected autoimmune disease. Other active malignancy in the last 5 years (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast). Prior treatment with anti-PD-1, anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen (CTLA-4), or anti-PD-L1 therapeutic antibody or pathway-targeting agents History of allergy to study drug components excipients Having any uncontrolled systemic diseases, including active infection, uncontrolled hypertension, diabetes, unstable angina, congestive heart failure, acte myocardial infarction (within 3 months before treatment), serious arrhythmia requiring drug treatment, liver, kidney and metabolic diseases Women in pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemotherapy plus pembrolizumab<br>Two to four cycles of neoadjuvant chemotherapy in combination with pembrolizumab will be administered before surgery, followed by another one to two cycles of chemotherapy plus pembrolizumab after surgery (4 cycles neoadjuvant/adjuvant chemotherapy in total ) then use pembrolizumab monotherapy for up to 1 year | Drug: Pembrolizumab<br>* Two to four cycles of neoadjuvant chemotherapy in combination with pembrolizumab will be administered before surgery, followed by another one to two cycles of chemotherapy plus pembrolizumab after surgery (4 cycles neoadjuvant/adjuvant chemotherapy in total ) then use pembrolizumab monotherapy for up to 1 year.<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MPR(major pathologic response) | more than 90 percent decrease in viable tumor | Up to 8weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete pathological (CPR) response rate | The investigator assessed CPR rate was defined as the percentage of subjects who achieved complete pathological remission (no residual tumor in lung and lymph nodes) | 8 weeks | 
| EFS (event free survival) | the time length from randomization (mainly from the receipt of pathology and genetic diagnosis reports)to any of the following events: disease progression, disease recurrence or death from any cause. Disease progression or relapse will be assessed according to RECIST 1.1 | 8 weeks | 
| OS (overall survival) | the time length from randomization (mainly from the receipt of pathology and genetic diagnosis reports)to death from any cause. | 8 weeks | 
| Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | Evaluate adverse events of any cause, treatment-related adverse events, immune-mediated adverse events according to NCI-CTCAE V5.0 | 8 weeks | 
| Evaluate tissue biomarkers | The goals for these analyses are for hypothesis generating. The results will need to be confirmed by future studies. Used for hypothesis generating. Transcriptome analysis identity markers with efficacy and/or toxicity. | 8 weeks |