A Phase III Trial of Neoadjuvant Sintilimab and Chemotherapy for NSCLC Harboring No Driver Mutations

Study Overview
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Brief Summary
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This is a randomized, open-label study designed to evaluate the safety and efficacy of neoadjuvant PD-1 antibody plus chemotherapy followed by surgery in resectable stage IIIA non-small cell lung cancer. The primary endpoint: pCR rate The second endpoint: MPR, DFS, MRD

Detailed Description
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This study is a prospective, multicenter, phase III randomized controlled clinical study. Stage IIIA NSCLC patients with EGFR mutation negative and ALK rearrangement negative were enrolled, and after 2 courses of treatment with Sintilimab combined with Platinum-based Chemotherapy, they were randomly assigned 1:1 to the control group (surgical resection and postoperative treatment for 2 courses are recommended) or the experimental group (surgery after 2 courses of treatment). The primary endpoint is pCR rate. The second endpoints are MPR, DFS, and MRD.

Official Title
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Neoadjuvant Sintilimab and Platinum-based Chemotherapy for Resectable Locally Advanced NSCLC Harboring no Driver Mutations: A Prospective, Randomized, Multicenter Phase III Trial

Conditions
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EGF-R Negative Non-Small Cell Lung Cancer, ALK Negative NSCLC, NSCLC, Stage IIIA

Intervention / Treatment
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* Drug: PD-1 and chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Resectable stage IIIA NSCLC, EGFR mutation-negative and ALK rearrangement negative (8th UICC TNM staging); No prior anti-tumor therapy for NSCLC; Age from 18 to 75 years old; Adequate organ function: Hemoglobin ≥9.0g/L; White blood cell count 4.0 10×109/L; The absolute value of neutrophils (ANC) ≥ 1.5×109/L; Platelet count ≥100×109/L; Total bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST≤2.5 times the upper limit of normal; The international normalized ratio of prothrombin time is ≤1.5 times the upper limit of normal value, and the partial thromboplastin time is within the range of normal value; Creatinine ≤ 1.5 times the upper limit of normal; No chemotherapy, radiotherapy or hormone therapy for malignant tumors, no history of other malignant tumors, excluding patients who have received hormone therapy for prostate cancer and have had DFS for more than 5 years; ECOG 0～1; Exclusion Criteria: Double primary or multiple primary NSCLC; EGFR mutation or ALK mutation was positive patients with psychosis; Pre-existing or coexisting bleeding disorders; Other uncontrollable and inoperable patients; Patients whose previous operations have prevented this operation from being performed; Female patients who are pregnant or breastfeeding; For patients who are allergic to the drugs in the program.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Neoadjuvant therapy of Sintilimab and chemotherapy in 2 cycles before surgery and optional adjuvant therapy of Sintilimab and chemotherapy in 2 cycles after surgery | Drug: PD-1 and chemotherapy<br>* Sintilimab+(Squamous)ABX+DDP/CBP, or (non-Squamous)PEM+DDP/CBP<br>|
| Experimental: Experimental group<br>Neoadjuvant therapy of Sintilimab and chemotherapy in 4 cycles before surgery | Drug: PD-1 and chemotherapy<br>* Sintilimab+(Squamous)ABX+DDP/CBP, or (non-Squamous)PEM+DDP/CBP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologically complete response (pCR) rate |  | in three weeks after the surgical resection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological response (MPR) rate |  | in three weeks after the surgical resection | 
| Disease-free survival (DFS) |  | one, two, three and five years since the initial treatment (each treatment is 2 days) | 
| Minimal residual disease(MRD) |  | in one week before each cycle and in the forth week after the surgical resection (each cycle is 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant, PD-1, NSCLC, Phase III, Platinum-based, Locally Advanced