Tislelizumab Combined With Chemotherapy as Neoadjuvant Therapy for Stage IIIA-IIIB (N2) Lung Squamous Cell Carcinoma

Study Overview
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Brief Summary
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Tislelizumab combined with chemotherapy has shown good efficacy and safety in clinical studies of lung adenocarcinoma (RATIONALE 304) and lung squamous cell carcinoma (RATIONALE 307), thus has been approved as the first-line therapy for advanced non-small cell lung cancer (NSCLC) in China. However, there is no data in the field of neoadjuvant therapy for NSCLC. This single-arm, single-center phase II clinical study is designed to evaluate the efficacy, safety and major pathological response (MPR) of Tislelizumab combined with chemotherapy as neoadjuvant therapy in patients with stage IIIA-IIIB (N2) lung squamous cell carcinoma. Biomarkers correlated with efficacy outcomes will also be explored.

Detailed Description
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Tislelizumab combined with chemotherapy has shown good efficacy and safety in clinical studies of lung adenocarcinoma (RATIONALE 304) and lung squamous cell carcinoma (RATIONALE 307), thus has been approved as the first-line therapy for advanced non-small cell lung cancer (NSCLC) in China. However, there is no data in the field of neoadjuvant therapy for NSCLC. This single-arm, single-center phase II clinical study intends to enroll about 30 patients with potentially operable lung squamous cell carcinoma with clinical stages IIIA-IIIB (N2). Participants will intravenously receive tislelizumab (BeiGene, 200mg d1) + albumin paclitaxel 260mg/m2 d1 + carboplatin AUC 5 d1, Q3W, Imaging evaluation is performed after 2 cycles of medication, and the feasibility of surgery is discussed in multiple disciplines. If the evaluation is operable, the lesion will be surgically removed 22-40 days after the last treatment. If it is assessed to be reduced but still inoperable, the original plan will be continued for another cycle. Imaging examinations, tissue NGS (whole-exome sequencing), gene expression profiling (GEP), and PD-L1 expression will be performed at baseline, preoperative and postoperative respectively.

Official Title
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Tislelizumab Combined With Albumin Paclitaxel + Carboplatin as Neoadjuvant Therapy for Patients With Stage IIIA-IIIB (N2) Lung Squamous Cell Carcinoma: A Single-arm, Single-center, Exploratory Phase II Clinical Study

Conditions
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Lung Squamous Cell Carcinoma, Neoadjuvant Therapy, Immunotherapy

Intervention / Treatment
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* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age is ≥18 years old and <75 years old. Eastern Cooperative Oncology Group (ECOG) physical status is 0 or 1. Untreated and histologically confirmed squamous cell lung carcinoma. Potentially operable stage IIIA-IIIB (N2) squamous cell lung carcinoma on enrollment (as defined by the American Joint Committee on Cancer 8th Edition). Sufficient pre-treatment tumor tissue samples/peripheral blood samples for biomarker analysis. Sufficient organ functions, including: Haematological status: absolute neutrophil count(ANC) ≥1.5×10^9 /L, platelet count(PLT) ≥100×10^9 /L, hemoglobin(HB) ≥90 g/L; Liver function: alanine glutamate transaminase (ALT) and glutamate transaminase (AST) ≤2.5 x upper limit of normal range (ULN), total bilirubin (TBIL)≤1.5 x upper limit of normal range (ULN); Kidney function: Creatinine(Cr)≤1.5 x upper limit of normal range(ULN) or Creatinine clearance ≥45 ml/min (calculated according to Cockcroft-Gault equation) Exclusion Criteria: Participants with known EGFR, ALK or ROS1 sensitive mutations. Participants with autoimmune diseases, tuberculosis, active hepatitis or HIV. Participants who are not expected to tolerate surgery, such as patients with cardiopulmonary insufficiency, etc. A history of other malignant tumors in the past 5 years, except for cured cervical carcinoma in situ, cured basal cell carcinoma of the skin and superficial bladder cancer [Ta, Tis & T1]. Participants who have used PD-1/PD-L1 and other immunotherapy drugs before. Women of childbearing age as the exclusion criteria.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab + Albumin Paclitaxel + Carboplatin<br>Tislelizumab 200mg d1, Albumin Paclitaxel 260mg/m2 d1, Carboplatin AUC5 d1, Q3W | Drug: Tislelizumab<br>* Participants received 2 cycles Tislelizumab 200mg d1 + Albumin Paclitaxel 260mg/m2 d1 + Carboplatin AUC5 d1 every 3 weeks, and then were evaluated for surgery.<br>* Other names: Carboplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Pathological Response (MPR) | Major Pathological Response (MPR) is evaluated after resection by pathologists, which is defined as a metric of ≤10% residual tumor tissue after neoadjuvant therapy. | 2-4 weeks after resection | 
| Incidence of Treatment-Emergent Adverse Events | Adverse events are evaluated by investigators according to CTCAE 5.0. | Through the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of radical resection (R0) | The rate of radical resection (R0) is evaluated by the investigator, which is the number of participants who can undergo R0 resection after the evaluation criteria established by the MDT team divided by the total number of enrolled groups. | 4 weeks after resection | 
| Overall Response Rate (ORR) | The overall response rate is evaluated by the investigator, which is defined as the percentage of patients with a best overall response of CR or PR relative to the appropriate analysis set (e.g. efficacy evaluable population) | 4 weeks after resection | 
| Disease-free survival (DFS) | Disease-free survival (DFS) is evaluated by the investigator, which is the percentage of individuals in the treatment group who are likely to be free of the signs and symptoms of a disease after a specified duration of time. | 1 year and 2 years after resection | 
| Overall survival (OS) | Overall survival (OS) evaluated by the investigator, which is the percentage of people in a group who are alive after a length of time. | Through the trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Squamous Cell Carcinoma, neoadjuvant therapy, immunotherapy