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

Immunotherapy Clinical Trial

— TACT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05024266
• Other study ID #: IIT20210011C-R1
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2021
• Est. completion date: August 31, 2023

Study information

• Verified date: August 2021
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Yujie Huang
• Phone: 0571-87236560
• Email: zyct79[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. The age is =18 years old and <75 years old.

2. Eastern Cooperative Oncology Group (ECOG) physical status is 0 or 1.

3. Untreated and histologically confirmed squamous cell lung carcinoma.

4. Potentially operable stage IIIA-IIIB (N2) squamous cell lung carcinoma on enrollment (as defined by the American Joint Committee on Cancer 8th Edition).

5. Sufficient pre-treatment tumor tissue samples/peripheral blood samples for biomarker analysis.

6. 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:

1. Participants with known EGFR, ALK or ROS1 sensitive mutations.

2. Participants with autoimmune diseases, tuberculosis, active hepatitis or HIV.

3. Participants who are not expected to tolerate surgery, such as patients with cardiopulmonary insufficiency, etc.

4. 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].

5. Participants who have used PD-1/PD-L1 and other immunotherapy drugs before.

6. Women of childbearing age as the exclusion criteria.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Immunotherapy
• Lung Squamous Cell Carcinoma
• Neoadjuvant Therapy

Intervention

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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital, Zhejiang University School of medicine	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence of Treatment-Emergent Adverse Events	Adverse events are evaluated by investigators according to CTCAE 5.0.	Through the trial
Secondary	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
Secondary	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
Secondary	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
Secondary	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