A Randomized, Double-blind, Placebo Controlled Phase III Study to Investigate Efficacy and Safety of First-Line Treatment With HLX10 + Chemotherapy (Carboplatin-Nanoparticle Albumin Bound (Nab) Paclitaxel) in Patients With Stage IIIB/IIIC or IV NSCLC

Study Overview
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Brief Summary
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This study is a randomized, double-blind, multicenter, phase III clinical study to compare the clinical efficacy and safety of HLX10 + chemotherapy vs chemotherapy in subjects with locally advanced or metastatic squamous NSCLC who have not previously received systemic treatment. Eligible subjects in this study will be randomized to Arm A or Arm B at 2:1 ratio as follows: Arm A (HLX10 arm): HLX10 + chemotherapy (carboplatin nab paclitaxel) Arm B (placebo arm): Placebo + chemotherapy (carboplatin nab paclitaxel) The three stratification factors for randomization include: PD-L1 expression level (Tumor Proportion Scores [TPS]≥50%, 50%>TPS≥1%, TPS<1%), Asian population (yes or no), NSCLC stage (stage IIIB/IIIC or stage IV), and carboplatin AUC (5 or 6).

Official Title
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A Randomized, Double-Blind, Multicenter, Phase III Clinical Study of HLX10 (Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection) + Chemotherapy (Carboplatin Nanoparticle Albumin Bound (Nab)-Paclitaxel) vs Chemotherapy (Carboplatin Nab-Paclitaxel) as First-Line Therapy for Locally Advanced or Metastatic Squamous Non Small Cell Lung Cancer (NSCLC)

Conditions
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Squamous Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: HLX10
* Drug: carboplatin and nab paclitaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed stage IIIB/IIIC and stage IV (AJCC Edition 8) squamous NSCLC where surgery or radiotherapy cannot be performed. No known sensitizing EGFR mutations or ALK, ROS1 gene rearrangements. Major organs are functioning well Participant must keep contraception Patients with prior denosumab use who can agree to switch to bisphosphonate therapy for bone metastases in the study. Exclusion Criteria: Patients with histologically non-squamous NSCLC. Mixed tumors will be classified according to the primary cell type. Patients do not meet the requirements for enrollment if small cell components and neuroendocrine carcinoma components are present. For non-small cell histology, patients meet the requirements for enrollment if squamous components (e.g., adenosquamous) are present. Patients with known history of severe hypersensitivity to any monoclonal antibody. Patients with known hypersensitivity to any compositions of carboplatin or nab-paclitaxel. Pregnant or breastfeeding females. Patients with a known history of psychotropic drug abuse or drug addiction; or a history of alcohol abuse. Patients who have other factors that could lead to the early termination of this study based on the investigator's judgment.

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>HLX10 + chemotherapy (carboplatin nab paclitaxel) | Drug: HLX10<br>* HLX10 is an innovative monoclonal antibody targeting PD-1，developed by Shanghai Henlius Biotech, Inc.<br>Drug: carboplatin and nab paclitaxel<br>* chemotherapeutics<br>|
| Placebo Comparator: B<br>Placebo + chemotherapy (carboplatin nab paclitaxel), After 1st PD, the subject will be unblinded by the investigator and be continued with HLX10 monotherapy | Drug: carboplatin and nab paclitaxel<br>* chemotherapeutics<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor assessment | Progression-free survival (PFS) (assessed by the independent radiology review committee [IRRC] based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) | Baseline until disease progression or death, whichever occurs first (up to approximately 24months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced or Metastatic, Squamous Non Small Cell Lung Cancer