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

Sponsor

First Affiliated Hospital of Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05024266

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Lung Squamous Cell Carcinoma Neoadjuvant Therapy Immunotherapy	Drug: Tislelizumab	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2021

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tislelizumab + Albumin Paclitaxel + Carboplatin Tislelizumab 200mg d1, Albumin Paclitaxel 260mg/m2 d1, Carboplatin AUC5 d1, Q3W	Drug: Tislelizumab Participants received 2 cycles Tislelizumab 200mg d1 + Albumin Paclitaxel 260mg/m2 d1 + Carboplatin AUC5 d1 every 3 weeks, and then were evaluated for surgery. Other Names: Albumin Paclitaxel Carboplatin

Arm

Intervention/Treatment

Experimental: Tislelizumab + Albumin Paclitaxel + Carboplatin

Tislelizumab 200mg d1, Albumin Paclitaxel 260mg/m2 d1, Carboplatin AUC5 d1, Q3W

Drug: Tislelizumab

Participants received 2 cycles Tislelizumab 200mg d1 + Albumin Paclitaxel 260mg/m2 d1 + Carboplatin AUC5 d1 every 3 weeks, and then were evaluated for surgery.

Other Names:

Albumin Paclitaxel

Carboplatin

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Rate of radical resection (R0) [4 weeks after resection]
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.
Overall Response Rate (ORR) [4 weeks after resection]
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)
Disease-free survival (DFS) [1 year and 2 years after resection]
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.
Overall survival (OS) [Through the trial]
Overall survival (OS) evaluated by the investigator, which is the percentage of people in a group who are alive after a length of time.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.