Clinical trial NCT05024266: Tislelizumab Combined With Chemotherapy as Neoadjuvant Therapy for Stage IIIA-IIIB (N2) Lung Squamous Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lung Squamous Cell Carcinoma
Neoadjuvant Therapy
Immunotherapy
Keywords: Lung Squamous Cell Carcinoma
neoadjuvant therapy
immunotherapy
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2021-08-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: 2-4 weeks after resection
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Through the trial
Secondary outcomes:
measure: Rate of radical resection (R0)
timeFrame: 4 weeks after resection
measure: Overall Response Rate (ORR)
timeFrame: 4 weeks after resection
measure: Disease-free survival (DFS)
timeFrame: 1 year and 2 years after resection
measure: Overall survival (OS)
timeFrame: Through the trial
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of medicine
state: Zhejiang
Study officials:
References: